Near-Infrared Light-Triggered Thermo-responsive Poly(N-Isopropylacrylamide)-Pyrrole Nanocomposites for Chemo-photothermal Cancer Therapy

Abstract

The combination therapy based on multifunctional nanocomposites has been considered as a promising approach to improve cancer therapeutic efficacy. Herein, we report targeted multi-functional poly(N-isopropylacrylamide) (PNIPAM)-based nanocomposites for synergistic chemo-photothermal therapy toward breast cancer cells. To increase the transition temperature, acrylic acid (AAc) was added in synthetic process of PNIPAM, showing that the intrinsic lower critical solution temperature was changed to 42 °C . To generate the photothermal effect under near-infrared (NIR) laser irradiation (808 nm), polypyrrole (ppy) nanoparticles were uniformly decorated in PNIPAM-AAc. Folic acid (FA), as a cancer targeting ligand, was successfully conjugated on the surplus carboxyl groups in PNIPAM network. The drug release of PNIPAM-ppy-FA nanocomposites was efficiently triggered in response to the temperature change by NIR laser irradiation. We also confirmed that PNIPAM-ppy-FA was internalized to MDA-MB-231 breast cancer cells by folate-receptor-mediated endocytosis and significantly enhanced cancer therapeutic efficacy with combination treatment of chemo-photothermal effects. Therefore, our work encourages further exploration of multi-functional nanocarrier agents for synergistic therapeutic approaches to different types of cancer cells.

Novel Multifunctional Stimuli-Responsive Nanoparticles for Synergetic Chemo–Photothermal Therapy of Tumors

“…11,41−43 The PA@nanogels are usually prepared by embedding or loading PA into nanogels or coating PA on the nanogel surfaces. Zhang et al 38 have prepared PA@nanogels by embedding noble gold nanorods (Au@SiO 2 ) inside temperature-sensitive poly(N-isopropylacrylamide) (PNI-PAM) nanogels; Meng et al 37 have prepared PA@nanogels by loading copper sulfide (CuS) semiconductor nanomaterials in the temperature-sensitive poly(2-(2-methoxy ethoxy) ethyl methacrylate-co-oligo(ethylene glycol) methacrylate) (MEO 2 MA@MEO 2 MA-co-OEGMA) nanogel networks; Shin et al 40 have prepared PA@nanogels by coating polypyrrole (PPy) on the surfaces of PNIPAM nanogels and modifying cell-targeting molecules via a condensation reaction. These PA@nanogels can release drugs under NIR laser irradiation to achieve synergistic chemo−photothermal therapy of tumors.…”

“…To date, several multifunctional responsive nanocarriers consisting of stimuli-responsive materials and photosensitive agents (PA) have been developed for synergetic chemo–photothermal therapy. According to the stimuli-responsive materials, they can be classified as PA@liposomes, , PA@micelles, , PA@polymeric nanochannels, − and PA@nanogels. − PA@liposomes and PA@micelles have some unavoidable problems unfortunately, such as structurally unstable, premature leakage of loading-drug when the environment changes, and uncontrollable sizes of particles. PA@responsive polymer nanochannels are usually prepared by grafting responsive polymers and fixing PA onto nanochannels (e.g., silica mesoporous substrates); however, the synthesis procedures are still somewhat complicated and the grafting products are usually uncontrollable to some extents.…”

Near-Infrared Light-Triggered Generation of Reactive Oxygen Species and Induction of Local Hyperthermia from Indocyanine Green Encapsulated Mesoporous Silica-Coated Graphene Oxide for Colorectal Cancer Therapy

“…In the spectra of ICG@MS-rGO-FA nanocomposite, two strong peaks were observed at 710 and 780 nm. The new peaks at 280 nm and 700–800 nm indicated the successful conjugation of FA and encapsulation of ICG in the nanocomposites [ 51 , 52 , 53 ]. Additionally, we calculated the loading efficiency of ICG in the rGO nanocomposites with or without MS based on the UV-vis absorption spectra (at 780 nm).…”

Poly(N-isopropylacrylamide)-Based Hydrogels for Biomedical Applications: A Review of the State-of-the-Art

“…Accordingly, systems such as, PNIPAM@ magnetic NPs (Fe 3 O 4 )/5-fluorouracil (5FU) and oxaliplatin (OXA)- acrylic acid (AA), 3-butenoic acid (3BA) or allylamine (AL) (pNIPAM@ Fe 3 O 4 /5FU/OXA-AA, 3BA, AL) [ 181 ], doxorubicin(DOX)-gold nanorods (GNRs)-PNIPAM@poly (d, l-lactide)-poly (ethylene glycol) (PLA-PEG) (DAPP)micelles (DOX-GNRs-PNIPAM@PEG-PLA,DAPP) [ 182 ], vancomycin (VANCO)/SF-Na Alg NPs/PNIPAM@epidermal growth factor (EGF) (VANCO/SF-Na Alg NPs/PNIPAM@EGF) [ 183 ], PNIPAM- superparamagnetic iron oxide nanoparticles (SPION)- etoposide (SPION-PNIPAM-Etoposide) [ 184 ], NaALG-g-P(NIPAM 80 - co -NtBAM 20 )/Dulbecco’s modified Eagle’s medium (DMEM) (NaALG-g-P(NIPAM 80 - co -NtBAM 20 )/DMEM) [ 185 ] and many more have been designed by researchers in order to intensify the use of PNIPAM polymer in the field of drug delivery [ 186 , 187 ]. Table 1 depicts the latest investigations of PNIPAM-based hydrogels in drug delivery.…”