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 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-bearing mouse models with significantly extended survival.

Recent progress in nanomedicines for imaging and therapy of brain tumors

“…In orthotopic GBM and GBM stem cell-bearing mouse models, these NIR-activatable biomimetic nanogels inhibit tumor growth with significantly increased survival. 196…”

“…With limited adverse effects, nanogels offer therapeutic options that overcome the BBB. [194][195][196] For example, using a pre-polymer process, a stimuli-sensitive nanogel was developed for efficient nanoirradiation delivery. At the tumor site, nanogel transcytosis is achieved by functionalization with a diphtheria toxin receptor ligand.…”

“…In orthotopic GBM and GBM stem cell-bearing mouse models, these NIR-activatable biomimetic nanogels inhibit tumor growth with significantly increased survival. 196 6 Theranostic nanomedicines for brain tumor Innovation is needed for the advanced diagnosis and treatment of brain tumors. When a single nanoparticle is used for both diagnostic and therapeutic purposes, it is known as ther- 190 Copyright permission © managed from (2017) American Chemical Society.…”

Emerging Strategies of Engineering and Tracking Dendritic Cells for Cancer Immunotherapy

“…144 Zhang et al provided a biomimetic nanogel system, synthesized by cross-linking pullulan and poly(deca-4,6-diynedioic acid) and loaded with temozolomide and indocyanine green (ICG); it can be activated by nearinfrared irradiation and deforms the cumulated nanogels to trigger burst drug release to achieve deep tumor penetration of drugs. 145 Combes et al thought the use of immune cells to deliver cancer vaccine deep within the TME could be a potential strategy. 146 In this context, DCs transfected with mRNA that can encode protein to target to tumor can be a potential antitumor vaccine.…”

“…Pandey et al designed linearly aligned nucleic acid-complexed polydixylitol-based polymeric nanochains (X-NCs), which can navigate through deeper regions of brain tumors via inherent hyperosmotic properties . Zhang et al provided a biomimetic nanogel system, synthesized by cross-linking pullulan and poly­(deca-4,6-diynedioic acid) and loaded with temozolomide and indocyanine green (ICG); it can be activated by near-infrared irradiation and deforms the cumulated nanogels to trigger burst drug release to achieve deep tumor penetration of drugs . Combes et al thought the use of immune cells to deliver cancer vaccine deep within the TME could be a potential strategy .…”