Acute myeloid leukemia (AML) is a highly aggressive form of leukemia. Researchers have studied the effect of cancer cells on platelet activation, and the proliferation and metastasis of cancer cells may be promoted by activated platelets. Platelet-derived microparticles (PMPs) account for 70
Lipid nanoparticles (LNPs) have emerged as the most clinically validated nanocarrier platform in oncology, transitioning from liposomal chemotherapy to the cornerstone of mRNA-based therapeutics. This review critically examines the evolving LNP landscape with a deliberate focus on p53, the tumour suppressor directly mutated or functionally silenced via pathway dysregulation in over half of human cancers and a unifying therapeutic target across diverse tumour types. We analyse LNP platform design, physicochemical properties, and structure-activity relationships that govern encapsulation, stability, and release. A dedicated section synthesizes p53-directed nucleic acid strategies delivered by LNPs, including p53 mRNA for wild-type restoration, siRNA for mutant p53 silencing, miR-34a mimics engaging the p53 downstream axis, and CRISPR-Cas9 components for TP53 correction. The review evaluates passive and active targeting, stimuli-responsive release mechanisms responsive to tumour microenvironmental cues, and the integration of p53 nanotherapy with immune checkpoint blockade. Clinical translation is appraised through key 2020–2026 milestones, notably the KEYNOTE-942 trial of personalized neoantigen mRNA-4157, which clinically validates the mRNA-LNP platform in oncology, alongside emerging preclinical and early exploratory p53 mRNA-LNP programs in hepatocellular carcinoma, non-small cell lung cancer, and pancreatic cancer. Persistent challenges, including liver-dominant biodistribution, anti-PEG immunogenicity, manufacturing scalability, and regulatory complexity, are discussed alongside artificial intelligence-guided lipid discovery and biomimetic approaches. By reframing LNP development around p53 biology, this review highlights how tumour-suppressor restoration offers a mechanistically coherent strategy to enhance therapeutic index, reprogram the tumour immune microenvironment, and extend LNP clinical benefit beyond the liver compartment across diverse tumour types. The synthesis indicates that p53-focused LNP engineering represents a convergent opportunity to unify diverse cancer nanomedicine efforts under a single, biologically grounded therapeutic paradigm.
Despite the recent progress in cancer treatment, the 5-year survival rates for many types of cancer are still below 30
Doxorubicin (Dox) is a potent chemotherapeutic agent for treating triple- negative breast cancer (TNBC), but its clinical utility is severely limited by non-specific biodistribution and dose-limiting systemic toxicity, particularly cardiotoxicity and nephrotoxicity. To address this clinical challenge, we developed hyaluronic acid (HA)-decorated PLGA nanoparticles co-loaded with superparamagnetic iron oxide (SPIO) and doxorubicin (HDSPs) and evaluated the potential of pulsed electromagnetic field (PEMF) guidance to enhance tumor-selective delivery. The platform integrates three targeting mechanisms: passive accumulation via optimal nanoparticle size and charge, HA-mediated engagement of the CD44 receptor, and PEMF-assisted magnetic guidance via SPIO. In CD44-positive MDA-MB-231 TNBC cells, HDSPs showed enhanced cellular internalization and intracellular doxorubicin delivery, and competitive blockade of CD44 with free HA reduced HDSP uptake, indicating a receptor-mediated component of internalization. PEMF exposure further increased intracellular iron uptake, whereas the accompanying differences in cell viability did not reach statistical significance. In TNBC xenograft models, localized PEMF application increased tumor accumulation of HDSPs by approximately 1.5-fold compared to non-PEMF treatment, with correspondingly lower signals in kidney and liver. The HDSP + PEMF system produced the greatest suppression of tumor growth among the groups tested, and no overt histopathological alterations were observed in heart or kidney at the dose and schedule used, in contrast to the changes seen after free doxorubicin. These findings suggest that combining HA-mediated CD44 engagement with PEMF-assisted magnetic guidance can improve tumor-selective doxorubicin delivery while limiting off-target exposure in TNBC, and support further evaluation of this strategy.
Breast cancer is the most common malignancy worldwide. Patients with advanced disease often experience recurrence and metastasis, driven by the immunosuppressive tumor microenvironment and resistance to PD‑1/PD‑L1 checkpoint therapy. To address these challenges, we developed a multifunctional nanoplatform named DMDD@MON‑Fe that integrates autophagy induction, immune modulation, and efficient therapy, and systematically evaluated its anti‑tumor efficacy and molecular mechanisms in breast cancer. Mesoporous organosilica nanoparticles (MON) were prepared using a one-pot template method. Iron species were introduced into MON through a heating-sublimation strategy to obtain MON-Fe, which was subsequently loaded with the natural small-molecule compound DMDD to form DMDD@MON-Fe. The nanoparticles were characterized by TEM, SEM, XPS, DLS, and BET. Their effects on breast cancer cell proliferation, migration, invasion, cell cycle, apoptosis, ROS, autophagy, and PD-L1/PD-1 expression were examined using MTT, colony formation, Transwell, flow cytometry, MDC staining, Western blot, and immunofluorescence. In vivo anti-tumor efficacy was evaluated in a subcutaneous syngeneic tumor model, and mechanisms and biosafety were explored via transcriptome sequencing, RT-qPCR, immunohistochemistry, TEM, and blood biochemical analysis. DMDD@MON-Fe showed a spherical morphology, pH-responsive drug release, and good hemocompatibility. In vitro, it significantly inhibited breast cancer cell proliferation, migration, and invasion, induced cell-cycle arrest, and promoted apoptosis and ROS generation. Mechanistically, DMDD@MON-Fe downregulated the PI3K/Akt/mTOR protein expression, activated autophagy, and suppressed PD-L1/PD-1 expression as shown by Western blot and immunofluorescence. In vivo, it inhibited tumor growth and induced autophagy and chromatin condensation (TEM). Transcriptomics revealed enrichment of differentially expressed genes in PI3K-Akt, autophagy, and immune-related pathways. H E staining and liver/kidney function tests confirmed excellent biosafety. DMDD@MON-Fe represents a promising iron-engineered mesoporous organosilica nanoplatform for enhancing DMDD delivery and antitumor efficacy in breast cancer. Its therapeutic effects are associated with increased ROS generation, suppression of PI3K/Akt/mTOR signaling, activation of autophagy, and inhibition of PD-L1 expression. These findings provide a potential nanomedicine-based strategy for improving DMDD delivery and alleviating PD-L1-associated immune suppression in breast cancer.
