In recent years, different drugs therapies for treatment pulmonary fibrosis (PF) have gained much attention due to development of drug delivery technology and urgent clinical needs. PF treatment existed a variety of currently clinical problem but PF could be treated with different drugs potentially though drug delivery technology. This review systematically expounds its basic theory, various drug delivery technologies, and future development directions. In the introduction, the relationship between the pathological mechanism of PF and drug delivery, the basic principles of the drug delivery system and the biological barriers faced by pulmonary drug delivery are analyzed. This review details delivery of small molecule drug, macromolecular drug and cells, including chemical synthesis and natural small molecule drug delivery, as well as RNA and cell-based delivery. Finally, the challenges and perspectives of these drugs to treat PF delivery technologies are discussed and key aspects in the development of PF drugs are considered. We hoped that this review can provide comprehensive and in-depth theoretical reference and technical support for the drug treatment of PF.

Malignant pleural effusion (MPE) is a serious disease caused by malignant tumors with high morbidity and mortality. Chemotherapy, immunotherapy, and antiangiogenic therapy are common treatments for MPE at present. However, traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients. The complex tumor microenvironment (TME) of MPE directly reduces the antitumor efficacy of immunotherapy. Fortunately, drug delivery systems (DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability, increasing the accuracy of tumor cell targeting, reducing toxic side effects, and remodeling TME, ultimately improving drug efficacy. Therefore, the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE. We discuss the application of biomaterials in the treatment of MPE from multiple perspectives, including chemotherapy, immunotherapy, combination therapy, and pleurodesis, where microspheres, cell membrane-derived microparticles (MPs), micelles, nanoparticles, and liposomes, are involved. The application of these biomaterials has been proven to have great potential in the treatment of MPE, providing a new idea for follow-up research.

A long-standing trade-off between fire safety and electrochemical performance in lithium-ion batteries arises from aggressive parasitic reactions between highly reactive flame retardants and electrodes. Herein, a phosphorus-fixed gel polymer electrolyte is constructed by covalently integrating 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO) into a vinylene carbonate-pentaerythritol tetraacrylate copolymer network through phosphorus-hydrogen addition. Covalent fixation confines DOPO within the gel matrix, delivering intrinsic flame retardancy while circumventing detrimental phosphorus-related side reactions. The abundant polar O=P–O moieties in DOPO not only promote lithium salt dissociation and provide additional coordination sites to facilitate rapid Li+ transport, but also actively reshape the Li+ solvation environment. Specifically, the DOPO-incorporated polymer tethers solvent molecules and restricts their entry into the primary coordination sheath, shifting the solvation equilibrium toward an anion‑dominated configuration. This solvation reconfiguration fosters LiF‑rich robust interphases on both electrodes, ensuring stable lithium deposition and exceptional oxidative stability. As a result, the as -prepared electrolyte achieves outstanding compatibility exceeding 3500 h against lithium anode, significantly enhanced cycling stability in LiFePO4, high-voltage LiNi0.8Co0.1Mn0.1O2 and LiNi0.9Co0.05Mn0.05O2-based full cells, as well as remarkable tolerance to flame, physical damage, and high-temperature operation. This work establishes a new paradigm for high-safety lithium-ion batteries, where phosphorus-based solvation engineering secures durable electrode interfaces under demanding conditions.

Bone remodeling, a highly regulated dynamic process critical for skeletal integrity and adaptability, is disrupted by pathological conditions such as fractures and osteoarthritis, leading to impaired bone structure and function. Although effective, traditional pharmacological treatments fail to fully restore native bone architecture. Biophysical stimuli exploit bone's mechanosensitivity to regulate bone cells via mechanotransduction, providing a targeted, physiological strategy for bone remodeling that complements conventional approaches. This review systematically examines how key biophysical signals regulate bone remodeling and discusses emerging therapeutic strategies that translate these principles into clinical applications, including mechanical, electrical, magnetic, acoustic, optical, and thermal stimuli. Recent advances in regenerative engineering have emphasized the incorporation of biophysical stimuli into advanced therapeutic platforms, including smart biomaterials, 3D-printed scaffolds, and wearable or implantable systems. Moreover, advanced preclinical screening tools, including bone organoids and bone-on-a-chip platforms, facilitate the systematic evaluation of biophysical interventions under physiologically relevant conditions, accelerating their clinical translation. By enabling the precise spatial and temporal control of stimulation, these approaches are designed to activate endogenous repair pathways and support coordinated regeneration across multiple biological scales, thereby offering promising strategies for treating severe bone disorders. By integrating fundamental mechanobiology with translational and engineering approaches, this review highlights the transformative potential of biophysical stimuli for treating bone diseases and advancing functional bone regeneration.

Osteoarthritis (OA), as a multifactorial degenerative joint disorder, is pathologically characterized by structural joint destruction and functional impairment, ultimately leading to chronic locomotor dysfunction. Clinically, intra-articular (IA) injection remains the preferred approach for localized OA treatment due to its advantages of high bioavailability, precise dosing, and minimal systemic side effects. However, frequent IA interventions may induce complications such as patient discomfort, pain, or even infection. Hydrogel materials, with their unique hydrophilic network structures and viscoelastic mechanical properties, are regarded as ideal joint cavity supplements and efficient drug carriers, making them a promising platform for localized therapy. This article systematically reviews recent advances in injectable hydrogel-based OA treatments. First, from a materials science perspective, it comprehensively analyzes the classification of injectable hydrogels (natural/synthetic polymers), their crosslinking mechanisms (chemical/physical/ionic), and environmental responsiveness (temperature/pH/ion triggers). Subsequently, it delves into their therapeutic potential in OA management, covering three major applications: controlled release of small-molecule drugs, cell delivery, and gene therapy. Despite the demonstrated prospects of hydrogels in OA therapy, attributed to their mechanical adaptability, biodegradability, and biocompatibility, key scientific challenges persist, particularly in maintaining IA mechanical homeostasis and long-term structural integrity. The review emphasizes that future research should focus on optimizing hydrogel architectures and enhancing delivery system functionalities to achieve sustained therapeutic efficacy in OA.

Polyvinylidene fluoride (PVDF)-based solid-state polymer electrolytes always suffer from their intrinsic flammability, limited Li+ transfer, and the interfacial degradation induced by high-activity residual N,N-dimethylformamide (DMF) solvent. Herein, a 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO)-anchored PVDF-based solid-state electrolyte is synthesized by a two-step reaction involving PVDF dehydrofluorination and subsequent phosphorus-hydrogen addition. The covalent immobilization of DOPO on PVDF polymers endows the electrolyte with high flame retardancy while inhibiting phosphorus-associated reactions with lithium anodes. The alteration in polymer crystallinity and polarity significantly increases the relative permittivity of electrolyte and leads to a densely-interconnected spherulite network, facilitating the homogeneous Li+ distribution and rapid transport. Remarkably, the DOPO-anchored polymers are involved in Li+ solvation at the expense of DMF molecules, which effectively suppresses DMF decomposition on electrode surfaces and promotes formation of a robust anion-derived solid electrolyte interphase. The resultant polymer electrolyte demonstrates exceptional cycling stability, maintaining over 2500 h in symmetric lithium cell (0.1 mA cm-2) and 850 cycles in LiFePO4/Li cells (0.5 C) with 94.27% capacity retention. Furthermore, it enables stable operation in high-voltage LiNi0.9Co0.05Mn0.05O2/Li and practical pouch cells, while achieving high safety of batteries under abusive conditions. This work presents an innovative design in PVDF-based polymer electrolytes for safe and long-cycling solid-state lithium-ion batteries.

Malignant pleural effusion (MPE) is a common complication of advanced malignancy with a median survival of less than 5 months. Intrapleural injection is the main treatment for MPE, but there are problems such as the concentration of drugs not being durable and stable in the thoracic cavity, limiting therapeutic efficacy, rapid metabolism of drugs leading to systemic toxicity, a single mechanism of drug. Esculentoside A (EsA) exhibits multi-targeted effects that are potentially valuable to improve the immunosuppressive microenvironment in the thoracic cavity and suppress the development of MPE. But the toxicity and short half-life of EsA severely limit its use. We have developed an EsA delivery system based on a temperature-sensitive hydrogel (PLEL) for local treatment of MPE by intrapleural injection. The EsA/PLEL hydrogel supported slow-release of EsA and maintained a stable intrathoracic drug concentration, which not only significantly inhibited the progression of MPE and prolonged survival, but also reduced the side effects of EsA. We found that downregulating of CXCL1/ CXCL2/CXCL3-CXCR2 axis expression to reduce tumour-associated macrophages (TAMs) infiltration and tumour angiogenesis was a potential molecular mechanism for EsA/PLEL hydrogel to control lung cancer MPE. Therefore, this EsA/PLEL hydrogel delivery system has high potential for intrapleural injection therapy of MPE.

Mid-low rectal cancer is one of the most common types of rectal cancer and has a poor prognosis. Surgery and chemoradiotherapy are the main treatments for early and advanced rectal cancer with an overall 5-year relative survival rate of only 56.9%. Development of novel antitumor agents is needed. Animal models of disease are indispensable for drug development. The most commonly used animal models of rectal cancer are established by inducing tumors by the subcutaneous transplantation, cecum or peritoneal injection, but not injection in the rectum. Their tumor microenvironment differs from that of rectal tumors in situ, which is hard to precisely simulate the occurrence and development process and drug response of human rectal cancer. In this study, we established orthotopic mouse models of mid-low rectal cancer with primary tumors originating from the rectum, including two models that could simulate the early and advanced stages of the disease, respectively. In the first model, the local primary tumor was restricted to the rectal area of the anal verge by rectal submucosal injection, its growth could be monitored with IVIS live imaging and magnetic resonance imaging. Histological analysis confirmed that the tumor originated from the submucosal layer and then invaded the muscular layer without metastatic tumors. This model may be useful for evaluating drugs for early mid-low rectal cancer in the future. The second model featuring a rectal primary tumor accompanied with abdominal metastases was established via rectal serosal injection. In this model, a large tumor formed at the rectal injection site and then metastasized to the abdominal cavity, reproducing the process from occurrence to metastasis of mid-low rectal cancer, and may be a good tool for the evaluation of drugs for advanced-stage disease. The injection methods used in these models do not require the aid of special colonoscopes, are simple and easy to operate, and have high tumor tumorigenicity and reproducibility. These results suggest that our staged modeling can provide targeted choices for preclinical drug research of mid-low rectal cancer at different stages.

Breast cancer is the most prevalent and lethal malignancy among females, with a critical need for safer and less invasive treatments. Photodynamic therapy (PDT) can effectively eliminate tumor cells with minimal side effects. Furthermore, the combination of PDT and immunotherapy using nanoparticles has shown promise in treating both primary and distant metastatic tumor cells. Therefore, this study proposes applying the PDT-immunotherapy combination to breast cancer treatment. However, the low immunogenicity characteristic of "cold" tumors in part of breast cancer significantly diminishes therapeutic efficacy. To address this challenge, here, a nano-gel system (designated as HCSC-gel) is constructed, which co-delivers a mitochondria-targeted photosensitizer and a STING agonist, capable of robustly activating "cold" tumor immunity. This system is further enhanced by collagenase (CN) to improve therapeutic outcomes. Upon injection into the primary tumor site, HCSC-gel rapidly forms a gel matrix, releasing CN to degrade the tumor extracellular matrix and facilitate the penetration of photosensitizers, STING agonists, and oxygen into the tumor tissue. Under laser irradiation, PDT and STING-mediated immune responses are activated, reversing the low immunogenicity of breast cancer and effectively treating both primary and metastatic lesions. This HCSC-gel nano hydrogel delivery platform is anticipated to provide novel insights for the clinical management of breast cancer and other low immunogenic "cold" tumors, offering significant benefits to patients.

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by the progressive breakdown of cartilage, which lacks the capacity for self-repair. However, the negatively charged nature and compactness of the extracellular matrix present obstacles for drugs administered via intra-articular injection to effectively permeate the cartilage matrix and reach the intended target sites. Despite advancements in drug delivery systems, achieving prolonged drug retention and efficient penetration into cartilage tissue remains a significant challenge. In response, this study presents a novel dual physiological signal-responsive KPP@PLEL nanohydrogel system designed to enhance cartilage repair by targeting bone marrow mesenchymal stem cells (BMSCs) and overcoming cartilage permeability barriers. The KPP@PLEL system uniquely combines a polyamidoamine (PAMAM) dendrimer modified with MMP-13 responsive peptides and kartogenin (KGN), which is encapsulated within a thermosensitive hydrogel, PLEL. This approach overcomes the limitations of previous delivery systems by leveraging both body temperature sensitivity and MMP-13 enzyme responsiveness, which are specifically upregulated in OA-affected tissues. This dual-response mechanism enables the sustained release and enhanced delivery of KGN to the deep cartilage matrix while maintaining extended retention in the joint cavity. In vitro and in vivo studies demonstrated that the KPP@PLEL system has excellent biocompatibility, effectively reduces inflammation, and promotes the differentiation of BMSCs into chondrocytes. Additionally, the system showed superior cartilage penetration and extended retention time compared with those of free KGN or the hydrogel alone. In vivo, significant improvements in cartilage regeneration and substantial reductions in osteoarthritis progression were observed following intra-articular administration. This research offers a promising dual-response nanohydrogel platform that addresses key challenges in osteoarthritis treatment by combining efficient drug delivery, prolonged retention, and potent regenerative effects.

Periodontitis, a prevalent chronic inflammatory disease, poses significant therapeutic challenges due to its complex pathological microenvironment. Current treatment strategies often fail to simultaneously address bacterial infection, microenvironment dysregulation and tissue regeneration. To overcome these limitations, we developed a novel ZnS/KAFAK@PLEL composite hydrogel platform for targeted periodontitis treatment. The engineered hydrogel exhibits a unique temperature-triggered sol-gel transition at body temperature, significantly prolonging its retention in periodontal pockets. In vitro studies demonstrate that the KAFAK (LAARLYRKALARQLGVAA) anti-inflammatory peptide effectively modulates cellular inflammatory responses, while ZnS nanoparticles scavenge reactive oxygen species (ROS), collectively promoting osteogenic differentiation of human periodontal ligament stem cells. Comprehensive antibacterial evaluations, including colony formation assays, live/dead staining, and bacterial morphological analysis, confirm the composite hydrogel with antibacterial performance against Porphyromonas gingivalis and Staphylococcus aureus. In a rat periodontitis model, the ZnS/KAFAK@PLEL hydrogel significantly attenuated alveolar bone resorption while enhancing bone mineral density and bone volume fraction. This multifunctional composite hydrogel combines anti-bacterial, anti-inflammatory and osteoinducible properties, demonstrating remarkable potential for clinical translation in periodontitis management.

Periodontitis is a chronic inflammatory disease caused by bacterial infection, leading to the destruction of periodontal tissues and impairment of oral function. The high-glucose microenvironment within periodontal pockets promotes the proliferation of pathogenic bacteria, worsening periodontal infections. Glucose oxidase (GOx)-like nanozymes can utilize elevated glucose levels locally to produce acid and hydrogen peroxide, aiding in infection control. Nevertheless, the catalytic efficiency of these nanozymes is low. Enhancing their activity may offer a promising approach for periodontitis treatment. Herein, we developed a NIR-driven hydrogel (AgZ@Au/PLEL) incorporating Au nanoparticles (Au NPs)-modified zeolitic imidazolate framework-8 (ZIF-8) loaded with Ag2S nanoparticles, aimed at treating periodontitis through antibacterial action and promotion of alveolar bone regeneration. The thermosensitivity and injectability of PLEL hydrogel ensured effective application in complex periodontal structures. The Au NPs exhibit GOx-like activity, catalyzing the decomposition of glucose in the periodontal pocket to produce acid and hydrogen peroxide. Upon exposure to near-infrared (NIR) laser irradiation, the catalytic activity of Au NPs is enhanced, resulting in increased hydrogen peroxide production that synergizes with photothermal therapy (PTT) for antibacterial effects. Meanwhile, the increased acid promotes ZIF-8 degradation, releasing zinc ions that stimulate alveolar bone regeneration. In vitro, laser-irradiated hydrogel exhibited potent bactericidal activity against periodontitis pathogens and promoted bone marrow stem cell differentiation. In vivo studies revealed that the NIR-driven nanosystem significantly enhanced treatment efficacy for periodontitis. Therefore, the NIR-driven GOx-like nanozyme-modified injectable thermoresponsive hydrogel offers a promising strategy for managing periodontitis

Postoperative adhesions are inevitable consequences of surgery, resulting in various complications. The risk increases, particularly in cardiac surgery, where reoperations or staged operations are in high demand. The presence of cardiac adhesions severely complicates resternotomy procedures, which may increase the risk of re-traumatizing, bleeding, operation time extension, and even mortality. Here, a biodegradable thermo-sensitive fouling-resistant hydrogel based on poly(D,L-lactide)/poly(ethylene glycol) (PLEL) micelles is developed, exhibiting high compatibility with both thoracotomies and minimally invasive interventions. By combining the advantages of liquid and film barriers, this hydrogel can completely cover irregular wounds after injecting or spraying and fully avoid direct contact with injuries between adjacent wound surfaces during the critical course of adhesion formation. In both the primary cardiac adhesion model and the severe repeated-injury cardiac adhesion model, the PLEL hydrogel is more effective than commercially available products (including Interceed film and sodium hyaluronate hydrogel) in significantly reducing the incidence and severity of adhesions, without causing any cardiac dysfunction or organ damage. The powerful anti-adhesion effect of PLEL hydrogel is closely related to its ability to inhibit the inflammatory response and balance the fibrinolysis system. This injectable and sprayable antifouling thermosensitive hydrogel represents a promising clinical solution for the prevention of postoperative and recurrent cardiac adhesion.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies. This is attributed to precise embolization and potent anti-tumor effect. However, certain limitations such as unstable loading, perfusion stasis, heterogeneous distribution, ectopic distribution, and insufficient dosage, restrict their clinical application. Herein, a novel personalized Y-90 carbon microsphere with high uniformity, high specific activity and high availability (90Y-HUACM) is presented. It is synthesized through planar molecular complex adsorption and chemical deposition solidification. 90Y-HUACM exhibited controllable size, excellent biocompatibility, outstanding in vitro and in vivo stability. The radiolabeling efficiency of Y-90 exceeded 99% and the leaching rate of Y-90 is far below 0.1%. Furthermore, the excellent anti-tumor effect, nuclide loading stability, anti-reflux characteristics, precise embolization, and biosafety of 90Y-HUACM were validated in a rabbit VX2 liver tumor model. In summary, this new, high-performance, and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.

The immerging three dimensional (3D) metal-organic framework (MOF)-reinforced composite solid-state electrolytes have attracted great interest because of the enhanced ionic conductivity and mechanical properties. However, the defective spatial arrangement of MOFs restricted by fabrication methodology leads to insufficient lithium ion transport in electrolytes. Herein, a 3D interconnected MOF framework tailored for all-solid-state electrolytes is rationally designed by a universal polydopamine (PDA)-engineered “double-sided tape” strategy. The PDA serves as a double-sided tape, firmly adhering on the special single-layer Nylon grid as well as offering uniform nucleation sites to anchor the metal nodes to ensure continuous growth of well-ordered MOFs. Benefiting from the Lewis acid feature of MOFs and its cage effect toward TFSI−, a fast and homogeneous lithium ion transport can be achieved through the internal channels within neighboring MOFs and the continuous MOFs/polymer interfaces both along the short-range circumferential boundary of Nylon fiber. The resultant composite electrolytes exhibit high lithium ion conductivity and prominent mechanical properties, rendering excellent cyclic stability whether used in coin or pouch cells. This work demonstrates a widely applicable “double-sided tape” strategy for controllable spatial arrangement of MOF nanoparticles on optional substrates, which provides a scalable approach to rationally construct desired lithium ion pathways within composite electrolytes.

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.

Camptothecin (CPT) exhibits potent antitumor activity; however, its clinical application is limited by significant gastrointestinal adverse effects (GAEs). Although the severity of GAEs associated with CPT derivatives has decreased, the incidence rate of these adverse effects has remained high. CPT multifunctional nanoparticles (PCRHNs) have the potential to increase the efficacy of CPT while reducing side effects in major target organs; however, the impact of PCRHNs on the GAEs from CPT remains uncertain. Here, we investigated the therapeutic effects of PCRHNs and different doses of CPT and examined their impacts on the intestinal barrier and the intestinal microbiota. We found that the therapeutic efficacy of PCRHNs + Laser treatment was superior to that of high-dose CPT, and PCRHNs + Laser treatment also provided greater benefits by helping maintain intestinal barrier integrity, intestinal microbiota diversity, and intestinal microbiota abundance. In summary, compared to high-dose CPT treatment, PCRHNs + Laser treatment can effectively balance therapeutic effects and GAEs. A high dose of CPT promotes the enrichment of the pathogenic bacteria Escherichia-Shigella, which may be attributed to diarrhea caused by CPT, thus leading to a reduction in microbial burden; additionally, EscherichiaShigella rapidly grows and occupies niches previously occupied by other bacteria that are lost due to diarrhea. PCRHNs + Laser treatment increased the abundance of Lactobacillus (probiotics), possibly due to the photothermal effect of the PCRHNs. This effect increased catalase activity, thus facilitating the conversion of hydrogen peroxide into oxygen within tumors and increasing oxygen levels in the body, which is conducive to the growth of facultative anaerobic bacteria.

The treatment of colorectal cancer is always a major challenge in the field of cancer research. The number of estimated new cases of colorectal cancer worldwide in 2020 is 1 148 515, and the estimated number of deaths is 576 858, revealing that mortality accounted for approximately half of the disease incidence. The development of new drugs and strategies for colorectal cancer treatment is urgently needed. Thermosensitive injectable hydrogel PDLLA-PEG-PDLLA (PLEL) loaded with cabazitaxel (CTX) is used to explore its anti-tumor effect on mice with orthotopic colorectal cancer. CTX/PLEL is characterized by a solution state at room temperature and a hydrogel state at physiologic temperature. The excipients MPEG-PCL and PDLLA-PEG-PDLLA have good biocompatibility and biodegradability. The simple material synthesis and preparation process renders this system cost-effective and more conducive to clinical transformation. An orthotopic colorectal cancer model is established by transplantation subcutaneous tumors onto the cecum of mice. According to the results of experiments in vivo, CTX/PLEL significantly inhibits orthotopic colorectal cancer and liver metastasis in mice. The results indicate that CTX/PLEL nanoparticle preparations have high security and excellent anti-tumor effects, and have great application potential in colorectal cancer therapy.

Colorectal cancer causes the third most common type of malignant tumors with high morbidity and mortality. Chemotherapy is currently one of the most effective and common treatments for colorectal cancer. However, the poor water solubility of some chemotherapeutics, untargeted drug delivery, and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer chemotherapy. Fortunately, drug delivery systems (DDS) based on biomaterials have been widely investigated and found to be capable of resolving those issues with good performance. Therefore, the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer chemotherapy. We not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics, including liposomes, micelles, and nanoparticles, but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus responses. Furthermore, locally administered systems based on hydrogels and microspheres, which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity, were also emphasized. DDS provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.