Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma

Dongya Zhang; Sidan Tian; Yanjie Liu; Meng Zheng; Xiangliang  Yang; Anne Zou; Bingyang Shi; Liang  Luo

doi:10.1038/s41467-022-34462-8

Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma

Dongya Zhang, Sidan Tian, Yanjie Liu, Meng Zheng, Xiangliang Yang, Anne Zou^*, Bingyang Shi^*, Liang Luo^*

^*Corresponding author for this work

Macquarie Medical School

Research output: Contribution to journal › Article › peer-review

92 Citations (Scopus)

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Abstract

Glioblastoma multiforme (GBM) is one of the most fatal malignancies due to
the existence of blood-brain barrier (BBB) and the difficulty to maintain an
effective drug accumulation in deep GBM lesions. Here we present a biomimetic
nanogel system that can be precisely activated by near infrared (NIR)
irradiation to achieve BBB crossing and deep tumor penetration of drugs.
Synthesized by crosslinking pullulan and poly(deca-4,6-diynedioic acid)
(PDDA) and loaded with temozolomide and indocyanine green (ICG), the
nanogels are inert to endogenous oxidative conditions but can be selectively
disintegrated by ICG-generated reactive oxygen species upon NIR irradiation.
Camouflaging the nanogels with apolipoprotein E peptide-decorated erythrocyte
membrane further allows prolonged blood circulation and active
tumor targeting. The precisely controlled NIR irradiation on tumor lesions
excites ICG and deforms the cumulated nanogels to trigger burst drug release
for facilitated BBB permeation and infiltration into distal tumor cells. These
NIR-activatable biomimetic nanogels suppress the tumor growth in orthotopic
GBM and GBM stem cells-bearingmouse models with significantly extended
survival.

Original language	English
Article number	6835
Pages (from-to)	1-16
Number of pages	16
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-34462-8
Publication status	Published - Dec 2022

Bibliographical note

Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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title = "Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma",

abstract = "Glioblastoma multiforme (GBM) is one of the most fatal malignancies due tothe existence of blood-brain barrier (BBB) and the difficulty to maintain aneffective drug accumulation in deep GBM lesions. Here we present a biomimeticnanogel system that can be precisely activated by near infrared (NIR)irradiation to achieve BBB crossing and deep tumor penetration of drugs.Synthesized by crosslinking pullulan and poly(deca-4,6-diynedioic acid)(PDDA) and loaded with temozolomide and indocyanine green (ICG), thenanogels are inert to endogenous oxidative conditions but can be selectivelydisintegrated by ICG-generated reactive oxygen species upon NIR irradiation.Camouflaging the nanogels with apolipoprotein E peptide-decorated erythrocytemembrane further allows prolonged blood circulation and activetumor targeting. The precisely controlled NIR irradiation on tumor lesionsexcites ICG and deforms the cumulated nanogels to trigger burst drug releasefor facilitated BBB permeation and infiltration into distal tumor cells. TheseNIR-activatable biomimetic nanogels suppress the tumor growth in orthotopicGBM and GBM stem cells-bearingmouse models with significantly extendedsurvival.",

author = "Dongya Zhang and Sidan Tian and Yanjie Liu and Meng Zheng and Xiangliang Yang and Anne Zou and Bingyang Shi and Liang Luo",

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AU - Zhang, Dongya

AU - Tian, Sidan

AU - Liu, Yanjie

AU - Zheng, Meng

AU - Yang, Xiangliang

AU - Zou, Anne

AU - Shi, Bingyang

AU - Luo, Liang

N1 - Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2022/12

Y1 - 2022/12

N2 - Glioblastoma multiforme (GBM) is one of the most fatal malignancies due tothe existence of blood-brain barrier (BBB) and the difficulty to maintain aneffective drug accumulation in deep GBM lesions. Here we present a biomimeticnanogel system that can be precisely activated by near infrared (NIR)irradiation to achieve BBB crossing and deep tumor penetration of drugs.Synthesized by crosslinking pullulan and poly(deca-4,6-diynedioic acid)(PDDA) and loaded with temozolomide and indocyanine green (ICG), thenanogels are inert to endogenous oxidative conditions but can be selectivelydisintegrated by ICG-generated reactive oxygen species upon NIR irradiation.Camouflaging the nanogels with apolipoprotein E peptide-decorated erythrocytemembrane further allows prolonged blood circulation and activetumor targeting. The precisely controlled NIR irradiation on tumor lesionsexcites ICG and deforms the cumulated nanogels to trigger burst drug releasefor facilitated BBB permeation and infiltration into distal tumor cells. TheseNIR-activatable biomimetic nanogels suppress the tumor growth in orthotopicGBM and GBM stem cells-bearingmouse models with significantly extendedsurvival.

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Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma

Abstract

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