Correction: Tumor acidity-responsive carrier-free nanodrugs based on targeting activation via ICG-templated assembly for NIR-II imaging-guided photothermal-chemotherapy.

Correction for 'Tumor acidity-responsive carrier-free nanodrugs based on targeting activation via ICG-templated assembly for NIR-II imaging-guided photothermal-chemotherapy' by Kaihang Xue et al., Biomater. Sci., 2021, DOI: 10.1039/D0BM01864C.

Tumor acidity-responsive carrier-free nanodrugs based on targeting activation via ICG-templated assembly for NIR-II imaging-guided photothermal-chemotherapy.

Carrier-free nanodrugs composed of photosensitizers and chemotherapeutic drugs show great potential in synergistic photothermal-chemotherapy. However, the targeting specificity to tumor cells is still a major obstacle for carrier-free nanodrugs. Meanwhile, almost all exogenous tumor-targeting ligands show no therapeutic effect by themselves. Here, a tumor microenvironment-driven self-targeting supramolecular nanodrug was successfully constructed via an indocyanine green (ICG)-templated small-molecule self-assembly strategy with methotrexate (MTX, folic acid-like antitumor drug) followed by post-insertion of weak acidity-responsive PEG for synergistic photothermal-chemotherapy. Interestingly, the size and morphology could be adjusted by changing the ICG-to-MTX ratio. Notably, the dynamic introduction of PEG not only could temporarily shield self-targeting function in blood to prolong the circulation time, but also could trigger the activation of self-targeting via re-exposing MTX ligands within the tumor microenvironment to enhance cellular uptake. Furthermore, the dePEGylated nanodrug would be disassembled to release MTX on-demand for chemotherapy via both stimuli of stronger lysosomal acidity and an external NIR laser. Moreover, the elimination of tumors could be realized through NIR-II fluorescence/PA imaging-guided synergistic photothermal-chemotherapy. The tumor microenvironment-driven carrier-free nanodrug based on self-targeting activation via ICG-templated assembly might provide a brand-new idea for synergistic photothermal-chemotherapy.

Ultralong-Circulating and Self-Targeting "Watson-Crick A = T"-Inspired Supramolecular Nanotheranostics for NIR-II Imaging-Guided Photochemotherapy.

A carrier-free theranostic nanodrug directly coassembled using a NIR probe and a chemotherapeutic drug is a promising alternative for cancer theranostics. Nevertheless, this nanodrug still faces the limitations of short blood circulation and inefficient tumor accumulation/tumoral cellular uptake in vivo. Meanwhile, most exogenous targeting ligands and poly(ethylene glycol) have no therapeutic effect. Herein, we designed an ultralong-circulating and self-targeting nanodrug by an ordered supramolecular coassembly of indocyanine green (ICG), methotrexate (MTX, chemotherapeutic drug and cancer-cell-specific ligand), and clofarabine (CA). Notably, CA, as a surfactant-like chemotherapeutic drug, was introduced into the initial ICG-MTX coassembly by "Watson-Crick A = T-inspired" hydrogen-bond-driven sequential assembly with MTX. This carrier-free theranostic nanodrug with exceptionally high drug payload (100 wt %) not only showed superior serum stabilities but also displayed ultralong blood circulation (>7 days), enabling efficient accumulation at tumor sites. Moreover, our nanodrugs could be self-recognized by cancer cells and release the drugs on demand through lysosomal acidity and external laser stimulus. Under NIR-II imaging guidance, high-efficiency tumor ablation via synergistic photothermal-chemotherapy could be achieved in one treatment cycle while preventing the tumor recurrence. Our ultralong-circulating and self-recognizing carrier-free theranostic nanodrug based on the "drug-delivering-drug" strategy might have the potential for clinical theranostic application.