Near-infrared Light Responsive Nanocarriers For Controlled Drug Release

Nowadays, there has been growing interest in lght-reponsive polymer because it could control over the moment and the location of drug release to provide a greater selectivity. Compared to other light(ultraviolet or visible light), near-infrared(NIR) light is a kind of long-wavelength light which shows less damage to irradiation area with a greater penetration depth of the skin and high spatial precision. This thesis has discussed three kinds of NIR responsive nanocarriers below:(1) We fabricated a new targeting NIR light responsive micelle for controlled drug release. The targeting NIR light-responsive copolymer(DDACMM-PEG-FA) was synthesized by polymerization of coumarin-containing monomer(DDACMM), poly(ethylene glycol)(PEG) methyl ether methacrylate and N-hydroxysuccinimide(NHS) and then modified by folic acid(FA). In vitro cell viability studies, the micelles exhibited higher intracellular DOX release under NIR irradiation at 808 nm, which resulted in significant growth inhibition of KB cancer cells.(2) We fabricated a new multifunctional nanovehicle for tumor therapy and cell imaging by coating the NIR light-triggered polymers(HAMAFA-b-DDACMM) onto the surface of octadecyltrimethoxysilane(C18)-modified hollow mesoporous silica nanopaticles(HMS@C18) via self-assembly. The copolymers could be disrupted by excitation of femtosecond NIR light laser(800 nm) via a two-photon absorption process due to the high two-photon absorption cross-section of the coumarin moiety. Under the excitation of NIR light at 800 nm, the pre-loaded drugs could be released from the nanocomposites due to the degradation of the light-responsive copolymers and the release efficiency was correlated with the irradiation time and light power. The in-vitro experiments indicated that the nanocomposites were easily targeted into the tumor cells that over-expressed folic acid receptor(FR(+)) such as KB cells by endocytosis. Furthermore, copolymer itself had strong fluorescence, which also provided a special way to track the process of drug delivery.(3) We fabricated a new multi-functional core-shell nanocarrier for near-infrared lightand p H-controlled drug release as well as magnetic resonance imaging(MRI) and fluorescence imaging. The core-shell nanocarriers(HPFe3O4@DDACMM-PEG-FA) were obtained by coating the amphiphilic copolymers onto the hollow porous ―core‖. Since the copolymer could be disrupted under the irradiation of NIR light laser(800 nm) via a two-photon absorption process, the pre-loaded drugs(~ 65%- 80%) could be released from the nanocarriers. What is more important, the subacid environment in tumour could further etch the boundary area of uncovered HPFe3O4, which further improved the efficiency of the drug release(about 20% increases in 24 h). The in vitro experiments indicated that the nanocarriers were biocompatible and could easily target into the tumour cells that over-expressed folic acid receptor(FR(+)) and release the pre-loaded drugs successfully. In addition, because of the superparamagnetism of HPFe3O4 and the fluorescence of polymer, the MRI and cell fluorescent imaging could be used to track the process of drug delivery.These NIR-light responsive nanocomposites will have potential performances in cancer therapy for their good biocompatibility and nice release efficiency.