Hypoxia-Responsive Lipid–Polymer Nanoparticle-Combined Imaging-Guided Surgery and Multitherapy Strategies for Glioma

Abstract

Glioma is the most prevalent type of malignant brain tumor and is usually very aggressive. Because of the high invasiveness and aggressive proliferative growth of glioma, it is difficult to resect completely or cure with surgery. Residual glioma cells are a primary cause of postoperative recurrence. Herein, we describe a hypoxia-responsive lipid polymer nanoparticle (LN) for fluorescence-guided surgery, chemotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT) combination multitherapy strategies targeting glioma. The hypoxia-responsive LN [LN (DOX + ICG)] contains a hypoxia-responsive component poly­(nitroimidazole)25 [P-(Nis)25], the glioma-targeting peptide angiopep-2 (A2), indocyanine green (ICG), and doxorubicin (DOX). LN (DOX + ICG) comprises four distinct functional components: (1) A2: A2 modified nanoparticles effectively target gliomas, enhancing drug concentration in gliomas; (2) P-(Nis)25: (i) the hydrophobic component of LN (DOX + ICG) with hypoxia responsive ability to encapsulate DOX and ICG; (ii) allows rapid release of DOX from LN (DOX + ICG) after 808 nm laser irradiation; (3) ICG: (i) ICG allows imaging-guided surgery, combining PDT and PTT therapies; (ii) upon irradiation with an 808 nm laser, ICG creates a hypoxic environment; (4) DOX inhibits glioma growth. This work demonstrates that LN (DOX + ICG) might provide a novel clinical approach to preventing post-surgical recurrence of glioma.

Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma

“…As the most aggressive and malignant tumor occurring in the brain, glioma is responsible for an enormous number of deaths in cases related to brain tumors around the world [ 17 ]. The promising advantages of low immunogenicity, intrinsic cell targeting properties, and enhanced stability in circulation make EVs an ever more attractive concept in targeted drug therapy, and highlight their potential in the therapy of various diseases, including glioma [ 12 ]. Recently, cell penetrating peptides have emerged as a critical player in targeted therapy for glioma by embellishing nanocarriers to deliver anti-tumor drugs [ 18 ].…”

“…Furthermore, bioluminescence and fluorescence imaging performed in a previous study confirmed the targeting ability of EVs-loaded PTX in neoplasia without adverse effects on other body tissues, which is highly suggestive of the therapeutic promise of systemic administration via EVs combined with chemotherapy agents [ 26 ]. ICG has been utilized in researches of the photothermal treatment of glioma [ 12 ]. In addition, ultrasound imaging-guided chemotherapy-hyperthermia induced by NIR light has been identified as a promising therapeutic modality against malignancies [ 27 ].…”

“…In addition, EV loading and surface modification play an important role in targeting the delivery of EVs encapsulated with therapeutic molecules or factors for the treatment of neurological disease [ 11 ]. Researchers have highlighted the huge potential of EVs in the therapy of various neoplasms, including glioma [ 12 ]. A previous report has elucidated that silk fibroin nanoparticles loaded with indocyanine green (ICG) in conjunction with near infrared (NIR) light for hyperthermia can kill residual glioma niche cells following surgical resection of the main tumor mass [ 13 ].…”

Polymer Pro-Drug Nanoparticles for Sustained Release of Cytotoxic Drugs Evaluated in Patient-Derived Glioblastoma Cell Lines and In Situ Gelling Formulations

“…We selected DOX as the drug candidate of first choice, due its use in multiple studies in vitro [18], in vivo [19] and human clinical trials [20,21], and its relevance in the treatment of GBM. Systemic injec-tion of free DOX, however, does not lead to high concentrations crossing the blood-brain barrier (BBB) [22], and so many researchers have utilised DOX-loaded NPs as a means to traverse the BBB [23][24][25]. For our studies, we wanted to evaluate whether localised delivery of polymer-DOX pro-drug NPs from the PEG-PLGA in situ gelling paste could avoid the issues of BBB transport while also allowing for transcytotic 'hopping' [26] of the NPs beyond the resection layer.…”

Active Targeting of Orthotopic Glioma Using Biomimetic Liposomes Co-loaded Elemene and Cabazitaxel Modified By Transferritin

“…Glioma is one of the most threatening disease to human with a high incidence and mortality rate in central nervous system tumors [1,2]. Up to now, chemotherapy is the most immediate and effective anticancer strategies for glioma due to the characteristic of heterogeneity, invasion and inability to be completely resected by surgical resection [3,4]. Chemotherapy in glioma, however, is usually hampered by selective penetrability of the blood-brain barrier (BBB), central nervous system toxicity and low targeting of drugs into the tumor site [5][6][7][8][9].…”