Sequence-Defined Nanotubes Assembled from IR780-Conjugated Peptoids for Chemophototherapy of Malignant Glioma.

Xiaoli Cai,Dan Du,Peng Mu,Tengyue Jian,Dong Liu,Yang Song,Mingming Wang,Yuehe Lin,Chun-Long Chen,Yanan Luo,Shichao Ding

doi:10.34133/2021/9861384

Abstract

Near-infrared (NIR) laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy. However, insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen (1O2) distribution over tumors from phototherapy results in tumor recurrence and inferior outcomes. To achieve high tumor killing efficacy, one of the solutions is to employ the combinational treatment of phototherapy with other modalities, especially with chemotherapeutic agents. In this paper, a simple and effective multimodal therapeutic system was designed via combining chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) to achieve the polytherapy of malignant glioma which is one of the most aggressive tumors in the brain. IR-780 (IR780) dye-labeled tube-forming peptoids (PepIR) were synthesized and self-assembled into crystalline nanotubes (PepIR nanotubes). These PepIR nanotubes showed an excellent efficacy for PDT/PTT because the IR780 photosensitizers were effectively packed and separated from each other within crystalline nanotubes by tuning IR780 density; thus, a self-quenching of these IR780 molecules was significantly reduced. Moreover, the efficient DOX loading achieved due to the nanotube large surface area contributed to an efficient and synergistic chemotherapy against glioma cells. Given the unique properties of peptoids and peptoid nanotubes, we believe that the developed multimodal DOX-loaded PepIR nanotubes in this work offer great promises for future glioma therapy in clinic.

Highlights

Photobased therapies such as photothermal therapy (PTT) and photodynamic therapy (PDT) have recently been developed as promising therapeutic strategies for antitumor therapy because of their minimal invasiveness, low side effects, and high specificity [1,2,3,4,5,6]
We developed a simple and effective multimodal therapeutic system against gliomas by using the CPT strategy, in which highly stable and crystalline peptoid nanotubes were used as the biocompatible scaffold to precisely display and align IR780 PSs and to simultaneously load chemotherapeutic drug doxorubicin (DOX)
PS-doped peptoid-based crystalline nanotubes, in which IR780 was attached at the N-terminus of tubeforming peptoid sequences, were coassembled and developed as an efficient platform to deliver DOX for the simultaneous chemo-PDT/PTT trimodal treatment of glioma

Summary

Introduction

Photobased therapies such as photothermal therapy (PTT) and photodynamic therapy (PDT) have recently been developed as promising therapeutic strategies for antitumor therapy because of their minimal invasiveness, low side effects, and high specificity [1,2,3,4,5,6]. For PTT and PDT, they usually utilize the near-infrared (NIR) laser-induced capability of photothermal agents and photosensitizers (PSs) to generate heat or cytotoxic singlet oxygen (1O2), which subsequently causes cell apoptosis [7,8,9,10]. Because of the nonuniform distribution of the near-infrared agents at the tumor site, the heat or cytotoxic 1O2 distribution over tumors is nonuniform. It leads to the insufficient tumor cell killing, incomplete ablation, tumor recurrence, and inferior outcomes [11, 12]. A tumor microenvironment- (TME-) responsive system PCPTSS/IR820 was designed by Shi et al.’s group for synergistic CPT [16].

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Conclusion