Products Cited in Publications Worldwide Nanochirality-programmed Type-I photosensitizer enables deep-tumor photodynamic therapy by reducing extracellular-matrix adhesion

Nanochirality-programmed Type-I photosensitizer enables deep-tumor photodynamic therapy by reducing extracellular-matrix adhesion

Liu, Yichen; Kim, Gaeun; Zhu, Runyao; Jeon, Hyunsu; Wang, Yichun

DOI:

Abstract

Tumor hypoxia and poor penetration of therapeutics across tumor-microenvironment barriers remain major obstacles to effective cancer therapy, including photodynamic therapy (PDT). Here we introduce a nanochirality-programmed assembly (L-Chi-GAIN) in which nanochirality drives site-selective assembly that activates oxygen-independent Type-I reactive oxygen species (ROS) generation and reduces hyaluronan-mediated matrix adhesion, thereby permitting deep intratumoral therapy. Glycosylation imparts structural chirality to graphene quantum dots (GQDs), directing site-selective assembly of indocyanine green (ICG) that turns on photoinduced electron transfer (PET), producing a 64-fold increase in ROS relative to free ICG. Nanochirality also modulates assembly–extracellular matrix (ECM) interactions. L-GQDs show a less favorable hyaluronan binding free energy (ΔGbind), thus accelerating interstitial transport and resulting in ∼21-fold deeper tumor penetration by L-Chi-GAIN than conventional nanocarriers. Under near-infrared irradiation, L-Chi-GAIN elicits strong oxidative stress and triggers Gasdermin-D (GSDMD)-dependent pyroptosis, leading to significant suppression of tumor growth. This work offers a nanochirality-guided design strategy for PDT in deep tumors by coupling site-selective assembly with stereoselective navigation of the ECM.

Keywords

Graphene quantum dot ; Solid tumor ; Type-I reactive oxygen species ; Chirality ; Extracellular matrix

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DSPE-mPEG (MW 2000)

A1159223147867-65-098% MW 2000

DSPE-mPEG (MW 2000)

29.0/250mg

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Indocyanine Green

A2013603599-32-495%

Indocyanine Green

53.0/100mg

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Acridine Orange base

A389055494-38-275%

Acridine Orange base

0.0/25g

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H2DCFDA

A4399064091-99-097%

H2DCFDA

20.0/1mg

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DPPC

A54259063-89-895%

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104.0/1g

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