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NBD Integrated and Vitamin B6-Driven Charge-Reversible Peptide-Based Nanocarriers for Targeted Therapeutic Delivery
Journal article   Peer reviewed

NBD Integrated and Vitamin B6-Driven Charge-Reversible Peptide-Based Nanocarriers for Targeted Therapeutic Delivery

Suman Nayak, Anushree Lye, Subhabrata Guha, Nanjundan Raghul, Adele Stewart, Gaurav Das, Biswanath Maity and Priyadip Das
Small (Weinheim an der Bergstrasse, Germany), e13436
02/07/2026
DOI: 10.1002/smll.202513436
PMID: 41653423

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Abstract

Peptide-based self-assembled nanostructures offer great promise for targeted drug delivery due to their intrinsic biocompatibility, biodegradability, and structural tunability. However, their limited optical properties and lack of functional sites for selective targeting restrict their use in theranostics. Here, we report a fluorophore-integrated, pH-responsive dipeptide nanocarrier engineered from phenylalanine-tryptophan (F-W) conjugated with 4-chloro-7-nitrobenzofurazan (NBD) as a fluorescent probe and vitamin B6 (VitB6) as a pH-sensitive unit. The resulting vitamin B6-modified nanoparticles (PS-Dox) exhibited charge reversal from negative to positive under mildly acidic conditions (pH 5.0), promoting doxorubicin (Dox) release, endosomal escape, and nuclear localization. PS-Dox demonstrated enhanced cytotoxicity, DNA damage, and apoptosis induction in multiple cancer cell lines, while showing negligible toxicity toward non-malignant cardiomyocytes (AC-16 and H9C2). In vivo biodistribution and pharmacokinetic studies revealed increased tumour accumulation and superior tumour growth inhibition compared with Dox. Importantly, PS-mediated encapsulation effectively mitigated Dox-associated cardiotoxicity, a major limitation of conventional chemotherapy. Overall, this study establishes a vitamin B6-mediated, charge-reversible peptide nanocarrier as a biocompatible and efficient platform for targeted anticancer drug delivery, combining tumour-specific therapeutic efficacy with improved cardiac safety.
Materials Science Physical Sciences Physics Technology Chemistry Chemistry, Multidisciplinary Chemistry, Physical Materials Science, Multidisciplinary Nanoscience & Nanotechnology Physics, Applied Physics, Condensed Matter Science & Technology Science & Technology - Other Topics

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