Nanoparticle Platforms in Cancer Immunotherapy: A Critical Comparative Review of PLGA, Mesoporous Silica, Magnetic Nanoparticles, and Covalent Organic Frameworks

Background/Objectives: Nanoparticle carriers can enhance cancer immunotherapy by improving tumor delivery, activating innate immune responses, and remodeling tumor microenvironments. This review evaluates four categories of formulations: poly(lactic-co-glycolic acid) (PLGA) nanoparticles, mesoporous silica nanoparticles (MSNs), magnetic or iron oxide nanoparticles (MNPs), and covalent organic frameworks (COFs). Methods: A reproducible PubMed audit identified 568 records. A rule-assisted title-and-abstract screen, followed by verification, removed 320 reviews, non-primary publications, and reports lacking qualifying in vivo formulation evidence. Of 248 potentially relevant reports, 15 primary studies were selected as representative examples; the remaining 233 were not classified as ineligible but were not selected as representative examples. These reports yielded 16 formulation-level records. One author conducted screening and extraction without protocol registration, duplicate review, or formal risk-of-bias scoring. Results: PLGA demonstrates the most robust polymer-level regulatory and manufacturing precedent; however, it remains limited by cargo instability, burst release, and challenges associated with process transfer. Biodegradable mesoporous silica nanoparticles (MSNs) facilitate pore-based protection and cytosolic delivery of cyclic dinucleotides, although their degradation and clearance are dependent on formulation specifics. Magnetic nanoparticles (MNPs) integrate magnetic targeting, imaging, and hyperthermia capabilities but necessitate formulation-specific magnetic characterization, field dosimetry, and repeated-dose safety assessments. Covalent organic frameworks (COFs) provide extensive stimulus-responsive and catalytic functionalities but exhibit the least mature evidence concerning biodegradation, scalable manufacturing, and independent reproducibility. Efficacy data across different studies were not pooled due to heterogeneity in models, schedules, comparators, and tumor-growth-inhibition formulas. Conclusions: The evidence does not endorse a universal platform ranking. Translation depends on standardized immune endpoints, explicit efficacy formulas, quantitative biodistribution assessments, mechanism-confirming experiments, repeat-dose toxicology studies, scalable manufacturing processes, and independent replication. The resulting evidence map serves as a descriptive and hypothesis-generating tool rather than a meta-analysis or clinical-priority scoring system.