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

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.

Methylene-Blue-Encapsulated Liposomes as Photodynamic Therapy Nano Agents for Breast Cancer Cells

“…Poly(carboxybetaine) modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-PCB) were synthesized via NHS-PCB-tBu conjugated with DPPE in accordance with our previous method [39] (structure was shown in Figure S1), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) (Avanti 850365, Alabaster, AL, USA), Methylene blue (MB) (Alfa-Aesar A18174, Lancashire, British), sodium dodecyl sulfate (SDS) (Acros Organics 230420250, Geel, Belgium), N , N -dimethyl-4-nitrosoaniline (RNO) (Sigma D172405, St. Louis, MO, USA), imidazole (Sigma I0250), Dulbecco’s modified Eagle’s medium−high glucose (DMEM-HG) (Thermo Hyclone SH30003.02, Waltham, MA, USA), fetal bovine serum (FBS) (Biological 04-001-1A), antibiotic-antimycotic solution (Penicillin/Streptomycin/Amphotericinβ, PSA) (Biological 03-033-1B), trypsin-EDTA (Biological 03-051-5B), 2′,7′-dichlorofluorescein diacetate (DCFH-DA ) (Sigma-Aldrich D6883, St. Louis, MO, USA), annexin V-FITC fluorescence microscopy kit (BD Pharmingen 550911), propidium iodide staining solution (PI) (BD Pharmingen 556463), and 1,1’-Dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (DiI) (Sigma 468495).…”

“…Liposomes were first introduced in the mid-nineteenth century, which were constructed of the lipid bilayer mimicking the cell membrane by using similar materials [37]. With a high biocompatibility and the ability to encapsulate either hydrophobic or hydrophilic pharmaceutic ingredients, liposomes are flexible and tunable in order to fit various uses [18,38,39,40]. In order to prolong the circulation half-life of liposomes, Polyethylene glycol treated (PEGylated) liposomes were developed, and they showed an enhanced blood circulation via bypassing digestive tract [41,42].…”

External and Internal Stimuli-Responsive Metallic Nanotherapeutics for Enhanced Anticancer Therapy

“…Recently, light-triggered phototherapy, which elevates the cellular temperature to kill cancer cells, was further investigated. Phototherapy significantly ablated tumors, inducing ICD, and reactivating cytotoxic immune cells against cancer (Rajendrakumar et al, 2018a ; Cherukula et al, 2019a , b ). Additionally, ultrasonic waves have been used to generate ROS and microbubbles, which interfere with cellular reactions and induce cancer cell death (Thomas and Kwan, 2019 ).…”

An On-Demand pH-Sensitive Nanocluster for Cancer Treatment by Combining Photothermal Therapy and Chemotherapy

“…To evaluate the feasibility of NC 2 for photothermal therapy, KB cells were studied considering the cancer located on the surface of the human body that can be treated by PTT [62,63]. The cell viabilities of NC 2 were evaluated for the synergistic effect of DOX and AuNR.…”