Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases.

Background/objective: Osimertinib, an EGFR-targeted agent approved for metastatic NSCLC, shows promise for triple-negative breast cancer due to EGFR overexpression in aggressive tumors. However, oral administration limits tumor delivery and causes systemic side effects. This study aimed to develop chitosan-coated PLGA nanoparticles loaded with osimertinib (CH-P-NPs) to enhance its anticancer efficacy in breast cancer cell lines (MDA-MB-231, MCF-7) by promoting apoptosis and reducing migration in vitro. Methods: CH-P-NPs were synthesized via single-emulsion solvent evaporation and characterized for particle size, zeta potential, encapsulation efficiency, and in vitro release. Anticancer activity was evaluated in MDA-MB-231 and MCF-7 cell lines through in vitro cellular uptake, cytotoxicity, apoptosis induction, and migration inhibition assays. Results: CH-P-NPs exhibited a particle size less than 200 nm, high encapsulation efficiency and a positive zeta potential. Moreover, sustained drug release was achieved with 59.62 ± 1.9% at 24 h. In vitro anticancer studies demonstrated that osimertinib and its nanoparticle formulations showed concentration-dependent cytotoxicity in MDA-MB-231 and MCF-7 cells. CH-P-NPs enhanced cytotoxicity compared with uncoated PLGA nanoparticles (IC₅₀: 1.56 vs. 6 µg/mL). CH-P-NPs enhanced cellular uptake in MDA-MB-231 cells, whereas its effect on MCF-7 cellular uptake was cell line-dependent. Annexin V/PI assay showed that CH-P-NPs significantly enhanced apoptosis compared to free osimertinib in both cell lines. In MDA-MB-231 cells, CH-P-NPs induced ~52.5% total apoptosis versus 3.3% with free drug. In MCF-7 cells, CH-P-NPs induced ~16.6% apoptosis versus 1.5% with free drug. Late apoptosis predominated, indicating irreversible cell death. Wound healing assay showed that CH-P-NPs significantly inhibited migration in both cell lines compared to free osimertinib and control. In MDA-MB-231 cells, CH-P-NPs exhibited greater inhibition at 48 and 72 h, while free osimertinib showed minimal effect. In MCF-7 cells, CH-P-NPs reduced migration at all time points. Conclusions: CH-P-NPs markedly enhanced osimertinib’s anticancer activity by improving cellular uptake, cytotoxicity, inducing apoptosis, and inhibiting migration. This nanoformulation offers a promising strategy to boost efficacy and reduce systemic toxicity in breast cancer treatment.