Engineered borate ester conjugated protein-polymer nanoconjugates for pH-responsive drug delivery

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery Systems

Background:

• Cytotoxic anticancer drugs like doxorubicin (DOX) face challenges in clinical efficiency and off-target side effects.
• Improved biocompatible and biodegradable drug delivery systems are needed for effective tumor cell penetration.

Purpose of the Study:

• To develop a novel doxorubicin-conjugated protein polymer nanoconjugates (PPNCs) prodrug delivery system.
• To enhance the clinical efficiency and targeting selectivity of doxorubicin while minimizing side effects.

Main Methods:

• DOX was conjugated to bovine serum albumin (BSA) and functionalized with lactobionic acid (LA) and folic acid (FA).
• BSA conjugates were linked to phenylboronic acid-functionalized poly(N-isopropylacrylamide) (PNIPAAm) via a pH-sensitive borate ester bond, forming PPNCs.
• In vitro studies evaluated the dose/time-dependent effects of PPNCs on MDA-MB-231 tumor cells.

Main Results:

• PPNCs demonstrated rapid accumulation in MDA-MB-231 tumor cells within 30 minutes, reaching maximum levels at 24 hours.
• A significant cell-killing effect was observed after 4 hours of incubation, with an IC50 of 0.5 mg/mL (approximately 4 μM/L).
• The constructed nanoconjugates exhibited efficient pH-dependent DOX release.

Conclusions:

• The developed PPNCs represent a promising strategy for targeted cancer therapy.
• These nanoconjugates offer improved drug delivery, enhanced tumor cell penetration, and reduced side effects.
• The pH-sensitive release mechanism of DOX from PPNCs contributes to their therapeutic potential.