Charge-Convertible Carbon Dots for Imaging-Guided Drug Delivery with Enhanced <i>in Vivo</i> Cancer Therapeutic Efficiency

TLDR

Carbon dots are promising nanocarriers, yet their therapeutic use is limited by surface properties that do not respond to the complex tumor microenvironment. The study develops a tumor‑extracellular‑microenvironment‑responsive cisplatin(IV) prodrug‑loaded charge‑convertible carbon dot nanocarrier for imaging‑guided drug delivery. The nanocarrier employs a dimethylmaleic acid‑modified PEG polymer that converts from anionic to cationic in mildly acidic tumor extracellular pH (~6.8), releasing positively charged CDs–Pt(IV) that bind strongly to cancer cell membranes, boosting uptake and cisplatin(IV) activation. In vitro and in vivo experiments demonstrate that the charge‑convertible nanocarrier achieves superior tumor inhibition with reduced side effects compared to non‑convertible controls, highlighting its potential for clinical cancer therapy.

Abstract

Carbon dots (CDs) are remarkable nanocarriers due to their promising optical and biocompatible capabilities. However, their practical applicability in cancer therapeutics is limited by their insensitive surface properties to complicated tumor microenvironment in vivo. Herein, a tumor extracellular microenvironment-responsive drug nanocarrier based on cisplatin(IV) prodrug-loaded charge-convertible CDs (CDs–Pt(IV)@PEG-(PAH/DMMA)) was developed for imaging-guided drug delivery. An anionic polymer with dimethylmaleic acid (PEG-(PAH/DMMA)) on the fabricated CDs–Pt(IV)@PEG-(PAH/DMMA) could undergo intriguing charge conversion to a cationic polymer in mildly acidic tumor extracellular microenvironment (pH ∼ 6.8), leading to strong electrostatic repulsion and release of positive CDs–Pt(IV). Importantly, positively charged nanocarrier displays high affinity to negatively charged cancer cell membrane, which results in enhanced internalization and effective activation of cisplatin(IV) prodrug in the reductive cytosol. The in vitro experimental results confirmed that this promising charge-convertible nanocarrier possesses better therapeutic efficiency under tumor extracellular microenvironment than normal physiological condition and noncharge-convertible nanocarrier. The in vivo experiments further demonstrated high tumor-inhibition efficacy and low side effects of the charge-convertible CDs, proving its capability as a smart drug nanocarrier with enhanced therapeutic effects. The present work provides a strategy to promote potential clinical application of CDs in the cancer treatment.