Biomimetic Shells Endow Sub-50 nm Nanoparticles with Ultrahigh Paclitaxel Payloads for Specific and Robust...

Area of Science:

• Nanomedicine
• Polymer Chemistry
• Oncology

Background:

• Current nanomedicine faces challenges in drug loading and tumor accumulation.
• Paclitaxel (PTX) is a key chemotherapy drug with limitations in delivery.

Purpose of the Study:

• To develop a novel core-shell nanoparticle (NP) platform for enhanced cancer therapy.
• To improve paclitaxel (PTX) delivery and reduce its associated toxicity.

Main Methods:

• Formulation of poly(ester amide) polymers with PTX and human serum albumin (HSA) complex.
• Characterization of optimized NPs (APP1i@e NPs) for size, loading, stability, and release.
• In vitro studies on cellular uptake, endosomal escape, and cytotoxicity.
• In vivo evaluation of pharmacokinetics, biodistribution, safety, and efficacy in ovarian xenograft models.

Main Results:

• Optimized APP1i@e NPs demonstrated small size (43.95 nm), high PTX loading (42.23%), and excellent stability.
• Acid-triggered release and efficient endosomal escape were observed in vitro.
• Surface PEGylation improved circulation time and targeting; HSA shell enhanced biosafety.
• APP1i@e NPs effectively inhibited tumor growth in vivo with reduced PTX toxicity.

Conclusions:

• The developed APP1i@e NPs offer a promising platform for improved cancer treatment.
• Surface PEGylation and biomimetic HSA design enhance NP performance for in vivo applications.
• This nanomedicine approach may significantly improve the therapeutic index of taxanes.