A Lipophilic IR-780 Dye-Encapsulated Zwitterionic Polymer-Lipid Micellar Nanoparticle for Enhanced Photothermal Therapy and NIR-Based Fluorescence Imaging in a Cervical Tumor Mouse Model.

Santhosh Rajendrakumar,In-Kyu Park,Ning-Chu Chang,Byeong-Il Lee,Adityanarayan Mohapatra,Wei-Bor Tsai,Saji Uthaman

doi:10.3390/ijms19041189

Abstract

To prolong blood circulation and avoid the triggering of immune responses, nanoparticles in the bloodstream require conjugation with polyethylene glycol (PEG). However, PEGylation hinders the interaction between the nanoparticles and the tumor cells and therefore limits the applications of PEGylated nanoparticles for therapeutic drug delivery. To overcome this limitation, zwitterionic materials can be used to enhance the systemic blood circulation and tumor-specific delivery of hydrophobic agents such as IR-780 iodide dye for photothermal therapy. Herein, we developed micellar nanoparticles using the amphiphilic homopolymer poly(12-(methacryloyloxy)dodecyl phosphorylcholine) (PCB-lipid) synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization. The PCB-lipid can self-assemble into micelles and encapsulate IR-780 dye (PCB-lipid–IR-780). Our results demonstrated that PCB-lipid–IR-780 nanoparticle (NP) exhibited low cytotoxicity and remarkable photothermal cytotoxicity to cervical cancer cells (TC-1) upon near-infrared (NIR) laser irradiation. The biodistribution of PCB-lipid–IR-780 showed higher accumulation of PCB-lipid–IR-780 than that of free IR-780 in the TC-1 tumor. Furthermore, following NIR laser irradiation of the tumor region, the PCB-lipid–IR-780 accumulated in the tumor facilitated enhanced tumor ablation and subsequent tumor regression in the TC-1 xenograft model. Hence, these zwitterionic polymer-lipid hybrid micellar nanoparticles show great potential for cancer theranostics and might be beneficial for clinical applications.

Highlights

Traditional therapies for cancer such as surgery, chemotherapy, and radiotherapy are invasive and nonselective treatment strategies that have notable side effects and poor treatment outcomes [1]
The absorbance spectrum of the IR-780 dye loaded in the PCB-lipid–IR-780 NPs showed a 15-nm redshift to 803 nm, indicating that hydrophobic dye inside the micelles experienced a change in polarity and hydrophobic interactions inside the micelles; and such a redshift demonstrated that IR-780 was efficiently loaded into the PCB-lipid micellar NPs rather than physically adsorbed onto the surface of the nanoparticles [7,14,15]
Our results revealed that PCB-lipid–IR-780 NPs could be a safe, highly efficient, and promising agent for in vivo photothermal therapy of TC-1 cervical cancer tumors

Summary

Introduction

Traditional therapies for cancer such as surgery, chemotherapy, and radiotherapy are invasive and nonselective treatment strategies that have notable side effects and poor treatment outcomes [1]. Alternative treatment methods such as photothermal or photodynamic therapies show enhanced spatiotemporal selectivity and minimal invasiveness [2]. Photothermal therapy (PTT) uses photoabsorbing materials that generate heat for tumor ablation upon near-infrared (NIR) laser irradiation [2]. Dye-based NIR-absorbing nanomaterials have theranostic properties and are used in NIR imaging and hyperthermic tumor ablation. Encapsulation of the IR-780 dye in amphiphilic micelle nanoparticles is expected to enhance its stability in aqueous solutions [4,5,6]. Ye Kuang et al encapsulated IR-780 dye in cyclic RGD-conjugated solid lipid nanoparticles and elucidated the enhanced NIR live-image-guided photothermal ablation of U87MG tumors [7]

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Discussion

Conclusion