Abstract Background: Sarcomas account for approximately 1% of adult cancers and 15% of childhood cancers in the United States. Conventional treatment strategies are somewhat effective during early disease, but once metastasized, treatment success significantly declines. Nanomedicine presents an alternative approach to increase current treatment efficacy and prolong survival. Optimization of liposomal preparations is essential to ensure the most selective targeting. The objective of the study was to develop a novel nanoliposomal drug delivery system using a cellular model of human clear cell sarcoma in vitro. Methods: The SU-CCS-1 cell line was selected as the cellular model for clear cell sarcoma and used for the drug selectivity studies. SU-CCS-1 cells were cultured and expanded in vitro for cellular extraction purposes. Cellular lipid extract (LE) material was derived from a clear cell sarcoma target (SU-CCS-1) cell line. Nanoliposomes were optimized for LE and cholesterol content. DPPE-Rhodamine (used as a fluorescence indicator) for cellular uptake studies, and a fluorescence microplate reader was used to assess relative fluorescence intensity values. Phase I of evaluation included characterization of cells and cellular uptake properties of nanoliposomal preparations of DOPC and cholesterol consisting of 0, 5, and 10 mol% cholesterol content. To characterize the cellular growth characteristics, separate flasks were prepared with either 100% adherent or 100% suspension cells acquired from a mature mixed cell population. The percentage of adherent and suspension cells was determined on Day 0 and Day 5. Results: An evaluation of growth profile characteristics of the SU-CCS-1 target cell line revealed a substantial transformation of suspension cells to adherent cells over time. While the flask of 100% adherent cells remained 72% adherent after 5 days, the flask of 100% suspension cells transformed to become 59% adherent after 5 days. The particle size for nanoliposomes containing 0, 5, and 10 mol% cholesterol was 283 nm, 139.9 nm, and 247 nm, respectively. Additionally, the inclusion of 10 mol% SU-CCS-1-LE increased uptake of nanoliposomes compared to 0% LE control preparations (without SU-CCS-1-LE). Conclusion: Preliminary findings suggest that the DOPC:cholesterol ratio affects nanoliposome uptake by SU-CCS-1 cells. The inclusion of SU-CCS-1-LE in nanoliposomes enhances their targeting efficiency. Ongoing studies will investigate the effect of dual incorporation of optimized cholesterol and SU-CCS-1-LE content on the targeting of clear cell sarcoma. Citation Format: Ashley Silva, Abigail Chan, Simoun Banoud, Charloote Bouchard, Robert B. Campbell. SU-CCS-1 lipid extract-modified nanoliposomes and characteristic growth profile of a model clear cell sarcoma target cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3030.

Abstract Background: Multiple myeloma (MM) is an incurable hematological malignancy characterized by the aberrant proliferation of plasma cells in the bone marrow. Current first line goals of therapy for newly diagnosed symptomatic MM aim to achieve minimal residual disease prior to transplant, a key predictor of overall survival. However, toxicities remain a rate limiting step during induction therapy. Cell membrane lipid-extracted nanoliposomes (CLENs) are a novel drug delivery system that can be optimized to preferentially target MM cells. Prior research involving the use of the multiple myeloma cell line, RPMI-8226, supports the use of lipid extracts (LE) to enhance targeting. This study aims to evaluate whether the inclusion of LE derived from an additional MM cell line, NCI-H929, will also enhance targeting, while decreasing nanoliposome uptake by model off-target and non-target cells. Methods: The MM (target) cell line explored in this study was NCI-H929. K562-GFP was used as the non-target cell line, and normal healthy peripheral blood mononuclear cells (PBMCs) served as the off-target cell control. Cells were seeded at a concentration of 20,000 cells/mL in vented centrifuge tubes and exposed for 1 hour to varying compositions of nanoliposome preparations including: DOPC, NCI-H929 lipid extract (LE), cholesterol (Chol), and DPPE-rhodamine for fluorescence studies. Nanoliposomes were prepared using a modified thin film method. Relative fluorescence intensity was determined using a fluorescence microplate reader. Results: Mean liposome diameters (± deviation) for DOPC formulations containing NCI-H929 LE were: DOPC (100%)- 188.6 ± 2 nm, DOPC/LE- 95/5 212.3 ± 2 nm, 90/10- 230.4 ± 2 nm, 85/15- 200 ± 4 nm, and 80/20- 142 + 1 nm. For formulations including cholesterol, diameters were: DOPC/Chol 90/10- 235 ± 2 nm and DOPC/Chol/LE 80/10/10- 227.4 ± 2 nm. Following 1 hour exposure of the target cell line to different concentrations of DOPC/LE, a statistically significant increase in uptake was observed in DOPC/LE preparations compared to DOPC alone: 95/5 and 90/10 (p < 0.0001), 85/15 (p < 0.001), and 80/20 (p < 0.05), with the highest uptake observed for 90/10. The addition of cholesterol did not further enhance uptake, and no significant uptake was observed in non-target or off-target cells compared to controls. Conclusions: Our preliminary findings support that cellular uptake in MM cells may be increased via NCI-H929-LE modified nanoliposomes, with diminished uptake by non-target and off-target cell populations. Confirmation studies are currently underway, including cytotoxicity studies comparing conventional chemotherapy against NCI-H929 LE-modified nanoliposomal formulations. Citation Format: Kenny D. Pham, Shivmani Barve, Robert B. Campbell. Enhancing targeted delivery in multiple myeloma via novel NCI-H929 lipid-extracted-modified nanoliposomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3024.

Abstract Introduction: Low-grade serous ovarian carcinoma (LGSOC) represents a rare subtype of epithelial ovarian cancer, accounting for less than 10% of all cases and typically diagnosed in younger women. The disease is characterized by tumor growth driven by activating mutations in the MAPK pathway, including KRAS, BRAF, and NRAS. Despite its slow progression, LGSOC remains challenging to treat due to limited responsiveness to conventional chemotherapy. The objective of this study was to isolate cellular lipid extract (LE) material from a model LGSOC cell line, and to utilize the newly acquired LE material to develop a relatively target specific nanoliposomal system. Early formulation and in vitro studies include optimization for cholesterol and LE content. Methods: Low-grade serous ovarian carcinoma cell line (PM-LGSOC-01, Cytion) was cultured and expanded in EMEM growth medium supplemented with 10% FBS. The PM-LGSOC-01-lipid extract (LE) material was extracted from PM-LGSOC-01 when the cells reached ∼90% confluency. Lipid extraction was performed as described previously (Alharbi & Campbell, AAPS Open, number: 5(2018)). Nanoliposomal preparations consisted of DOPC, cholesterol, and LE at various ratios and wereformed by thin film method using a Buchi R-80 rotary evaporator. DPPE-Rhodamine was included in the preparations for cellular studies. Following sonication, particle size and zeta potential values weredetermined using ZetaPals. Fluorescence detection was performed using a fluorescence microplate reader. Results: Three preparations (1) DOPC (100%), (2) DOPC/Chol (95/5), and (3) DOPC/Chol (90/10) wereprepared with an average particle size of 221 ± 3 nm, 250 ± 5 nm, and 139 ± 0.3 nm, respectively. Preliminary results suggest that the additional inclusion of cholesterol in the nanoliposomal preparations increased their uptake by the target (PM-LGSOC-01) cells. Studies investigating the influence of PM-LGSOC-01-LE on the uptake of nanoliposomes by the target cells are currently underway. Conclusion: To date, the influence of cholesterol on the uptake of nanoliposomes by LGSOC cells has been investigated. Future studies will evaluate the effect of optimized cholesterol and LE contenton targeting low-grade serous ovarian carcinoma. Citation Format: Sofia Orlando, Krishna Panchal, Heer Patel, Robert B. Campbell. Cellular uptake of nanoliposomes with optimized cholesterol concentration and lipid extract derived from a model low grade serous ovarian carcinoma cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3027.

Abstract Background: Lipid Nanoparticles (LNPs) have been established as excellent vehicles for drug/nucleotide delivery for Chronic Myeloid Leukemia (CML). The optimization of lipid ratios of cationic and helper lipids, such as phosphatidylcholine (PC) and phosphoethanolamine (PE)- based lipids, governs the selectivity of LNPs. Furthermore, the incorporation of LE (lipid extracts) derived from target cell membranes has been used to develop CLENs (cell membrane lipid-extracted nanoliposomes) for superior targeting. However, the behavior of PE- and PC-based lipids in the presence of LE is not well understood. In this study, we investigate the cellular interactions of LNPs consisting of PE or PC phospholipids employed in different combinations of cationic lipids and/or lipid extract ingredients using a model CML (K562-GFP) cell line. Methods: The K562-GFP human CML cell line (CCL-243-GFP) was cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS). LNPs were prepared using the thin film hydration method and characterized for size and zeta potential. Phase I of the study compared the cellular uptake of LNPs, substituting four cationic lipids (DOTAP, EPC, DOTMA, DODMA) at varying concentrations (0-50 mol%) with the helper lipid DOPC. Phase II involved comparing the PC versus PE helper lipid at a fixed cationic lipid concentration determined in Phase I. Phase III of the study aims to investigate the cellular uptake of LNPs after the inclusion of LE at various concentrations by target and non-target cell lines. Results: We identified the cellular uptake to be about 250% higher for LNPs containing 25 mol% of DOTAP or EPC compared to the control (DOPC 100 mol%) from Phase I. Phase II revealed that LNPs with helper lipid DOPC performed significantly better at all time points (0 to 120 min) with an increase in cellular uptake compared to helper lipid DOPE. In phase III, the inclusion of LE derived from the target cell in the cationic LNPs led to a selective uptake by the target cell line and decreased uptake by the non-target cell lines. Conclusion: Results to date revealed that the cellular uptake of LNPs depends largely on the optimum ratio of the cationic lipid to the helper lipid type employed in the development of the nanoparticles, and that inclusion of LE leads to superior targeting. Citation Format: Shivmani Y. Barve, Robert B. Campbell. Investigating phosphatidylcholine and phosphoethanolamine phospholipids in conventional and novel cationic nanoliposomes for interactions with chronic myeloid leukemia cells in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3028.

The author has identified an error in the author's name in an article titled "An Overview of Conventional Drugs and Nanotherapeutic Options for the Treatment and Management of Pediatric Acute Lymphoblastic Leukemia," published in Anti-Cancer Agents in Medicinal Chemistry, 2022, 18, 3050-3061 [1]. Details of the error and a correction are provided here. ORIGINAL: Andre Yohan1 1Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, 19 Foster Street, Worcester, MA 01608, USA CORRECTED: Andre Yonan1 1Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, 19 Foster Street, Worcester, MA 01608, USA We regret the error and apologize to readers. The original article can be found online at: https://www.benthamscience.com/article/122906.

Abstract Background: Lung cancer causes substantial cancer deaths in the U.S. Drug resistance remains a major issue. Nanoliposomes demonstrate enhanced drug targeting and resistance-overcoming potential. Incorporating lipid extracts derived from target cells shows improved delivery over conventional nanoliposomes. This study examined the effects of lung cancer cell lipid extract nanoliposomes against target and non-target cell populations from different environments. Method: Cellular Membrane Lipid-Extracted Nanoliposomes (CLENs) were fabricated with DOPC, DOTAP, ChaGo-K-1 lipid extract, cholesterol, PEG5000, and rhodamine fluorescent label was incorporated for uptake studies. The liposome size was reduced by probe sonication. Particle size and polydispersity index (PDI) were measured by dynamic light scattering. Zeta potential was quantified by laser Doppler micro-electrophoresis. Four cell lines were utilized: ChaGo-K-1 NSCLC target, A549 pulmonary microenvironment control, 4T1 extra-pulmonary control, and normal lung fibroblasts off-target control. All cell lines were cultured in 48-well plates at a seeding density of 10,000 cells/mL and incubated for 24 hours. Freshly prepared CLENs were added to all cell lines and incubated for an additional 24 hours. Cells were washed with PBS, and fluorescence intensity was then quantified and qualified by a microplate reader to measure the cellular uptake of the CLENs. Results: The mean particle size and PDI of the ChaGo-K-1 CLENs were 117 ± 0.7 nm and 0.216 ±0.009, compared to 126 ± 0.5 nm and 0.195 ± 0.008 for the control, respectively. Both formulations were within the optimal size range for drug delivery and tumor cell penetration. The zeta potential of the ChaGo-K-1 CLENs was -1.75 ± 1.81 mV compared to -1.74 ± 6 mV for the control. Quantification and qualification of cellular uptake using fluorescence intensity measurements revealed a 3.2-fold increase in ChaGo-K-1 CLENs compared to conventional liposomes without ChaGo-K-1 lipid extracts. This demonstrates that the inclusion of the lipid extracts in the CLEN significantly enhanced selectivity and delivery to target cancer cell populations. Conclusion: Higher uptake occurred with target cells using CLENs with lipid extracts versus standard liposomes. NSCLC-derived CLENs show potential to improve selective delivery and overcome drug resistance. Further, in vivo studies evaluating selective NSCLC tumor accumulation and efficacy enhancement are warranted. Citation Format: Mohammed Alqaryan, Rashad Allahyani, Dayeoun Lee, Robert B. Campbell. Overcoming lung cancer drug resistance: Enhanced cellular delivery using lipid-extracted nanoliposomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3196.

Abstract Background: Pancreatic cancer is a challenging type of cancer to treat as evidenced by a 9% 5-year survival and a dismal rate of mortality. Nanoparticles represent a revolutionary treatment method, primarily due to characteristics including cellular absorption, boosting therapeutic effectiveness, and mitigating side effects through localized actions. For nanomedicine, optimizing liposome formulations is crucial for achieving the highest level of specificity in drug targeting. This study aims to evaluate cellular interaction of pancreatic cancer lipid-extract modified nanoliposomes when compared to unmodified varieties in vitro. Method: Cell membrane lipid-extracted nanoliposomes (CLENs) were prepared via the thin film evaporation technique. The composition included various compositions and ratios of DOPC, DOTAP, Cholesterol, DPPE-PEG-5000, and lipid extracts derived from MS1-VEGF target cells. MS1-VEGF was the cellular model of pancreatic cancer used for this study. Cellular binding studies were performed using cellular suspension and adherent cell populations. Studies were performed in 48-well plates under different experimental conditions including alterations in time of incubation, and periods of cellular exposure to dual humidified and oscillation environments in the presence of lipid-extracted (LE) nanoliposomal preparations and conventional controls. Results: The particle size for nanoliposomes employed for this study was approximately 115 ± 0.7 nm for control and 128 ± 2.7 nm for experimental (lipid extract-modified) nanoliposomes. Following cellular exposure to different lipid extract concentrations (typically 0 to 100 nmoles per ml of growth medium), the fluorescence values demonstrated increased cellular uptake with greater LE content for floating and adhered MS1-VEGF cell populations. With the floating cells, LE-modified nanoliposomes demonstrated significantly higher fluorescence intensity values compared to conventional nanoliposomes. Similarly, with MS1-VEGF adherent cells, LE-modified nanoliposomes targeted cells to a greater extent compared to unmodified controls. Conclusions: The increased cellular uptake of CLENs designed for targeting pancreatic tumor cells (both floating and adherent cells) demonstrated an improvement over the use of conventional nanoliposomes under similar experimental conditions. Further research is needed to fully explore the potential use of CLENs for targeting and treatment of pancreatic cancer. Citation Format: Khaznah Alshammari, Sergio Verdery, Sujin George, Robert B Campbell. Assessing the utility of cell membrane lipid-extracted nanoliposomes (CLENs) as a targeted drug delivery system for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3200.

Abstract Background: Glioblastoma Multiform (GBM) is an aggressive and malignant form of brain cancer known for its invasiveness and significant heterogenicity. The majority of GBM cases are linked to genetic mutations (ie. TP53, EGFR, and PTEN), which disrupt the normal regulation of cell growth and division, resulting in uncontrolled cell proliferation. The utilization of nanoparticles presents a promising approach for addressing the complexities associated with selective drug delivery to GMB and treatment. The purpose of this study was to investigate the effect of including U87-MG membrane lipid extracts in nanoliposomes using target, non-target, and normal healthy cellular populations in vitro. Methods: The nanoliposomes employed for the experiments included various ratios of U87-MG lipid extracts (lipids derived from U87-MG cells), DOPC, Cholesterol, and DPPE-Rhodamine for fluorescence studies. The particle size and zeta potential values were measured and monitored throughout for consistency. Fluorescence intensity values (arbitrary units) were used to assess extent of cell binding, and uptake at the various time points. In vitro studies were employed to evaluate the cellular uptake activity of U87-MG-modified nanoliposome preparations using mixed ratios and compositions of lipid materials. Cell lines employed were, LN-18 (human glioma), T98G (human glioma), U87-MG (human glioma), 4TI (murine breast), and HBEC-5i (normal healthy) cells. Results: The average size for the nanoliposomes (with and without lipid extract) fell within the range of 110 to 220 nm, while the zeta potential for the CLENs was negatively-charged. In vitro studies revealed that the inclusion of U87MG lipid extract in nanoliposomes increased cellular uptake in glioma cells when compared to control. Current investigations focus on different microenvironments, including non-target and off target cell populations. The findings from the cellular uptake analyses to date suggest that the in vitro cellular uptake of the CLENs varied in accordance with the total lipid extract content for all cell lines. Citation Format: Kaylee Janton, Duha Baamir, Aesha Patel, Sheren Boco, Robert Campbell. Targeting cellular models of glioblastoma versus non-target and off-target cell populations using U87-MG membrane lipid-modified nanoliposomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2046.

Abstract Background: Every breast cancer diagnosis is unique in its own way. Triple-negative breast cancer (TNBC), has a highly aggressive phenotype characterized by a rapid growth rate profile, increased risk of metastasis and recurrence. TNBC is devoid of epidermal growth factor receptor 2, estrogen, and progesterone receptors. All three are commonly present in other forms of breast cancer disease. The aim of this study was to develop a cell membrane lipid-extracted nanoliposomes (CLENs) for selective targeting compared to conventional nanoliposomal varieties. An additional objective was to investigate the role of microenvironment on targeting using cell model of TNBC, and representations of non-target tissue environments for comparison. Method: Lipid extracts (LE) obtained from 4T1, a murine mammary carcinoma cell line from a BALB/cfC3H mouse was used to formulate the CLENs (cell membrane lipid-extracted nanoliposomes) with different ratios of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), a phospholipid used in most conventional drug delivery liposomes. Different lipid compositions and ratios were employed to evaluate cellular uptake in target, non-target and off-target cells. The target cell line, 4T1, off-target and non-target cell populations included CRL-2089, normal breast fibroblasts, SKBR3 a (human breast cancer), and A549 a (lung cancer) cell lines. Other studies involved determination of molecular charge and zeta potential of various nanoliposomal preparations and corresponding fluorescence studies in vitro. Results: The physicochemical properties of CLENs such as particle size and surface charge characteristics were vital when assessing benefit of the lipid-based preparations. The size of the CLENs typically ranged between 130 - 165 nm and zeta potential values were negatively-charged. The inclusion of 70 mol% of LE in preparation of 4T1-CLENs demonstrated increased cellular uptake and binding by the 4T1 target cells compared to the control DOPC (100%). The highest degree of selectivity was observed in early cell binding events, and with studies involving more extended incubation time points under different experimental conditions. Off-target cells demonstrated reduced uptake by comparison. Overall, 4T1-CLENs was most efficient when applied against intended target 4T1 cells, when compared to relevant control cell populations. In conclusion, studies performed to date suggest the notion that lipid extracts derived from TNBC improves targeting. Citation Format: Christiana Ayertey, Parmida Amid, Mohammed H. Almozain, Robert B. Campbell. An analysis of breast cancer membrane lipid-modified nanoliposomes for enhanced targeting of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3198.

Chronic myeloid leukemia (CML) is a blood cancer predominantly affecting older adult patients. According to the American Cancer Society, an estimated 8,860 people will be diagnosed with CML in 2022. Treatments for CML have evolved with a focus on CML phase severity or progression. Overall, there have been some breakthrough treatment options for a high percentage of patients with CML. This is largely due to the discovery of tyrosine kinase inhibitors (TKI); however, drug resistance continues to present a significant challenge in the management of CML disease. The use of interferon (IFN), antimetabolites, and bone marrow transplants provides alternative treatment options, but also presents limitations, including severe side effects, toxicity, and graft versus host disease. Nanomedicine has demonstrated benefits in terms of efficacy, often reducing or eliminating unwanted toxicities associated with the use of conventional drug agents. This review summarizes rational molecular targets of CML drugs and provides highlights of current FDA-approved agents for the treatment of CML. Additionally, this communication includes an overview of the limitations of conventional treatments and how nanomedicine has addressed challenges encountered during CML treatment.

According to the American Cancer Society, the prevalence of lymphoma remains high in the United States with an estimated 90,390 new cases, and 21,680 deaths annually. Although current chemotherapeutic regimens approved by the FDA can effectively improve treatment outcomes, the prognosis remains poor with numerous complications. Current therapeutic strategies have faced multiple challenges limiting desired therapeutic effects. With the multitude of clinical barriers faced by conventional treatment strategies, researchers continue to explore the use of nanotherapeutics over more conventional treatment options. The engineered nanoparticles include starting materials from a number of biocompatible sources, and the final products can safely incorporate therapeutic agents, improve drug selectivity to tumor targets, and enhance efficacy profiles, all while reducing toxicity associated with the drug payload. These are tremendous potential advantages. This review summarizes the molecular basis of lymphoma, disease progression, and therapeutic challenges encountered during treatment. The discussions further highlight preclinical and clinical results at the different clinical stages, reviewing the different types of lymphoma, and summarizing how nanotherapeutics have addressed challenges confronting treatment.

Background: Multiple myeloma (MM) is a plasma cell malignancy that primarily affects the elderly. MM is the second most common hematologic cancer with approximately 25,000-30,000 new cases diagnosed annually in the United States. A challenge associated with MM therapy is unwanted drug uptake by normal healthy cells. Nanoparticles provide a promising outlook to mitigate these issues, offering more selective drug uptake, while minimizing toxicity associated with treatment. The objective of this study was to develop, optimize and evaluate physicochemical and In vitro properties of MM-CLENs in comparison to conventional liposomes and relevant cell controls. Methods: RPMI-8226 MM cell line was selected cellular model for MM disease. RPMI-8226 cells were cultured and expanded In vitro for cellular extraction purposes. Lipid extraction (LE) procedures were performed to generate the RPMI-8226 LE ingredient. Other lipid ingredients used in preparation of RPMI-8226 CLENs included DOPC, cholesterol, and DPPE-Rhodamine (fluorescence indicator). Phase I included physicochemical characterization and cellular uptake studies of CLENs preparations with varying concentration of RPMI-8226-LE (0 to 40 mol%) content. Phase II began with the optimized concentration of LE determined in Phase I, along with varying concentrations of cholesterol (0 to 40 mol %) content for the nano-targeting studies in vitro. The control cell lines represent other hematological diseases, K-562-GFP (chronic myeloid leukemia), CCRF-CEM (acute lymphoblastic leukemia), and U937 (lymphoma). Results: Phase I and II physicochemical characterization and In vitro studies, revealed that the optimized preparation of RPMI-8226-CLENs consisted of 5% LE, and 5% cholesterol content. Optimal preparation consisted of DOPC: Cholesterol: LE (90:5:5) with an average values for particle size and zeta potential of 178±38 nm (n=4), and -14±4 mV (n=4), respectively. The inclusion of LE in conventional DOPC:cholesterol liposomes resulted in significantly improved uptake of the CLENs by RPMI-8226 cells in vitro (P< 0.001). However, preliminary selectivity studies suggest no significant difference in the uptake of RPMI-8226-CLENs by RPMI-8226 when compared to control cells (K-562-GFP, CCRF-CEM and U937). Conclusion: Studies involving RPMI-8226 CLENs are currently underway. Such studies include target selectivity, and influence of additional components of CLENs as a function of the microenvironment. Citation Format: Christina T. Tran, Eden Park, Pedro L. Rodriguez-Flores, Robert B. Campbell. Evaluation of cell membrane lipid-extracted nanoliposomes (CLENs) as a potential drug platform for targeting multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 237.

Retinoblastoma is the most common type of eye cancer in infants and children. Probability of saving vision and survival depends upon two main factors: progression of the disease from unilateral to bilateral and severity of the disease. In order to effectively treat retinoblastoma and retain vision, it is crucial to focus treatment options on reducing toxicity and nonspecific targeting while enhancing drug delivery, cellular uptake, and accumulation of chemotherapeutic agents to their specific target sites. Rapid elimination from blood circulation is the greatest obstacle that conventional chemotherapeutic agents face on journey to their target sites. Target specific nanoparticles have proven to be a useful tool in efforts to overcome challenges typically encountered by targeting strategies. Development of nanoparticles loaded with chemotherapeutic agents can allow for more selective tumor targeting, extended drug circulation times, and reduced drug-associated toxicity. Nanoparticles can significantly improve the treatment efficacy in retinoblastoma. The purpose of this review is to discuss the important characteristics and differences of nano delivery systems used against cellular and in vivo models of retinoblastoma, particularly as they relate to the popular Y79 retinoblastoma cell line.

: Acute lymphoblastic leukemia (ALL) is a common form of pediatric cancer affecting the lymphoblast, a type of white blood cell found in the bone marrow. In this disease, the normal lymphoblast cells transform into leukemic cells and subsequently enter the bloodstream. Leukemic cells found in patients with ALL have shown differences in cholesterol uptake and utilization. Current treatment consists of chemotherapy, chimeric antigen receptor (CAR) therapy, and hematopoietic stem cell transplantation (HSCT). In addition, minimal residual disease (MRD) has become an effective tool for measuring treatment efficacy and the potential for relapse. : Chemotherapy resistance remains a significant barrier in the treatment of ALL. Biomarkers such as an upregulated Akt signaling pathway and an overexpressed VLA-4 integrin-protein have been associated with drug resistance. Nanoparticles have been used to favorably alter the pharmacokinetic profile of conventional drug agents. These drug-delivery systems are designed to selectively deliver their drug payloads to desired targets. Therefore, nanoparticles offer advantages such as improved efficacy and reduced toxicity. : This review highlights conventional treatment options, distinctive characteristics of pediatric ALL, therapeutic challenges encountered during therapy, and the key role that nanotherapeutics play in the treatment of ALL.

Extensive studies have explored potential therapies against multiple myeloma (MM), whether in hospitals, universities, or in private institutional settings. Scientists continue to study the mechanism(s) underlying the disease as a basis for the development of more effective treatment options. There are many therapeutic agents and treatment regimens used for multiple myeloma. Unfortunately, no cure or definitive treatment options exist. The goal of treatment is to maintain the patient in remission for as long as possible. Therapeutic agents used in combination can effectively maintain patients in remission. While these therapies have increased patient survival, a significant number of patients relapse. The off-target toxicity and resistance exhibited by target cells remain a challenge for existing approaches. Ongoing efforts to understand the biology of the disease offer the greatest chance to improve therapeutic options. Nanoparticles (targeted drug delivery systems) offer new hope and directions for therapy. This review summarizes FDA-approved agents for the treatment of MM, highlights the clinical barriers to treatment, including adverse side effects normally associated with the use of conventional agents, and describes how nanotherapeutics have overcome barriers to impede conventional treatments.

Highly selective drug targeting is an important goal in the development of cancer nanotechnologies. In an effort to improve tumor targeting a method was developed to formulate cell membrane lipid-extracted nanoliposomes (CLENs). The main ingredients were extracted directly from the membrane of cancer cells. For this study we used three different breast cancer cell lines (4 T1, BT-20, and SK-BR-3). As controls for the normal breast and cancer tissue environments we employed the normal breast fibroblast (CRL-2089) and ovarian cancer (SK-OV-3) cell lines, respectively. We evaluated physicochemical properties, efficiency of drug loading, cellular uptake, and cytotoxicity. The mean diameter and zeta potential values for the 5 different CLENs were 202 ± 38 nm and − 15 ± 3.8 mv, respectively. Doxorubicin hydrochloride (5 mol%) increased the size of 4 T1-CLENs from 158 ± 2 nm to 212 ± 59 nm, with no significant change in the negatively-charged surface potential. Percent of drug loaded ranged from 40 to 93%, varying according to the ratio of lipid extract to conventional components employed. The additional inclusion of cholesterol and DPPE-PEG 5000 increased drug loading in CLENs, similar to Doxil preparations. The most promising cellular uptake and cytotoxicity profiles were observed when the lipid ingredients were derived from the eventual target cell. Given the ability of CLENs to better recognize target cells compared to nanosystems consisting of non-specific lipid extracts or conventional liposome ingredients alone, CLENs has demonstrated early promise as a nano-delivery system for cancer treatment.

One of the longstanding issues limiting the use of chemotherapeutic agents is the lack of tumor specificity, which leads to systemic toxicity. Therefore, various targeted nanocarriers have been developed to concentrate the cytotoxic drug agents at tumor regions to avoid uptake by normal healthy tissues. Previous studies from our laboratory have demonstrated that cell membrane lipid-extracted nanoliposomes (CLENs) are capable of selective targeting compared to nanoliposomes consisting of mainly conventional lipid materials. Also, CLENs were relatively nontoxic when employed at concentrations traditionally used to evaluate nanoparticles in vitro. However, parameters such as lipid composition, size, and surface charge all have a direct impact on liposomal cellular uptake. In this study, we prepared different CLENs different molar ratios of natural and cellular-derived lipids extracted directly from breast cancer cells (4T1), cholesterol, and DPPE-PEG-5000. The formulations were used to investigate the mechanisms of CLENs uptake and determine the underlying mechanisms regulating cellular entry. In the study, CLENs were used to evaluate cytotoxicity and cellular uptake for both target and off-target cell populations. CLENs containing cholesterol and DPPE-PEG-5000 (70/25/5) were able to retain doxorubicin in relevant therapeutic concentrations. CLEN formulations were able to exert selective cytotoxic drug effects against different target breast cancer cells in vitro. 4T1 CLENs containing cholesterol and DPPE-PEG-5000 (70/25/5) demonstrated greater binding to 4T1 (target) cells compared to CLENs prepared using 4T1 lipid extracts alone. The binding was not only temperature- and time-dependent, but also composition- and cell type-dependent. Off-target effect studies showed that 4T1 CLENs were taken up minimally by off-target cells (including normal breast fibroblasts and normal myocytes), compared to controls. Our studies collectively support the use of lipid extracts derived from target cells for selective drug targeting and enhanced cytotoxicity. Future studies will explore underlying mechanisms of cellular entry and cardioprotective function. Citation Format: Hanan M. Alharbi, Robert B. Campbell. An evaluation of breast cancer cellular membrane lipid-extracted nanoliposomes (CLENs) in relation to formulation design, stability, mechanism of cellular entry and cardioprotective function in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4666.

Designing an effective nanoparticle for selective drug transport requires careful consideration of the complex biological barriers encountered in transit to the desired target. Here, we review several of these barriers, and provide possible methods for formulating liposomal nanoparticles to overcome them. The methods include the biotinylation of an antibody, and subsequent conjugation to a PEGylated cationic lipid nanoparticle. Additionally, the incorporation of drug, and other relevant characteristics of the nanoparticle are also discussed.

Nanotechnology has brought about the advent of personalized medicine in the era of targeted therapeutic strategies for cancer therapy. The ability to exploit tumor features for therapeutic gain has made it possible to manufacture more effective nanomedicines for cancer treatment. However, known obstacles, including the inability to overcome pathophysiological barriers of tumors, have impeded disease management. In spite of this, recent efforts have been made to develop more functionalized nanosystems that utilize the active-targeting approach. This article reviews the FDA-approved cancer drug delivery systems in the general framework of personalized nanomedicine. We discuss the latest efforts in the development of functionalized nano-systems, and summarize relevant ongoing preclinical and clinical trials.