Construction Of Multifunctional Polymeric Nanospheres And The Anti-cancer Research

In recent years, with the rising incidence of cancer, the development of new cancer treatment method has important significance. Traditional treatment methods include surgery, radiotherapy and chemotherapy, while new treatment methods are hyperthermia, photodynamic therapy, immunotherapy and so on. These methods play an important role in tumor treatment, but there are still great challenges in tumor suppression. Therefore, the combination of two or more cancer treatment means to fight against cancer, become the hot issue in present research. Combination therapy based on the experience of clinical practice, is also dependent on the versatility of medical materials designed to meet the different needs of cancer treatments.With the development of nanoscience, nanotechnology has been increasingly applied in the field of biomedicine. Gold nanorods with surface plasmon resonance, and their special radiation and non-radiation characteristics, are expected to become a new type of nanomaterials for the applications in biological and biomedical fields, including biosensing, biomedical imaging, gene and drug transportation, disease detection, diagnosis and treatment. Gold nanorods are easily induced to general hyperthermia by the near-infrared light close to the wavelength of its longitudinal plasma resonance absorption peak, so they have special advantages on the thermal therapy of tumor. Because near-infrared light has capability of deep tissue penetration, near-infrared laser as a light source can heat up the gold nanorods in deep subcutaneous tissue. Therefore, gold nanorods have been demonstrated to be promising in diagnosis and photothermal treatment of cancer cells in the deep subcutaneous tissue.In this work, we prepared size controllable and stable hybrid nanospheres by using chitosan as matrix material to complex gold nanorods. Combined with chemotherapy drugs and photodynamic drug respectively, the combination therapy of thermal therapy/chemotherapy or thermal therapy/photodynamic therapy is established to examine the synergic effect of them and their anti-tumor effect. For the photodynamic therapy, the therapeutic agents can be endogenously stimulated by chemluminescence of tumor imaging through hydrogen peroxide, a signal molecule of tumors, in which the medical diagnosis and treatment are combined together. Specific work contents are as follows:(1) In the aqueous solution, chitosan with low molecular weight is water-soluble and positive charged, while ethylenediamine tetraacetic acid (EDTA) is negatively charged. With the aid of the poor solvent of ethanol, they can efficiently package and complex gold nanorods to form the chitosan-gold nanorods (CS-AuNR) hybrid nanospheres through electrostatic complexation. Antitumor drug cisplatin is loaded on the shell matrix of chitosan to afford multi-function chitosan-gold nanorods-cisplatin (CS-AuNR-Pt) hybrid nanospheres. We focus on the synergic effect of gold nanorods and cisplatin, and their antitumor effects. This work provides a multifunction nanospheres carrier for combination of thermotherapy and chemotherapy treatment.(2) Photodynamic drugs, indocyanine green, is loaded on the shell matrix of the CS-AuNR hybrid nanospheres through electrostatic adsorption, to form chitosan-gold nanorods-indocyanine green (CS-AuNR-ICG) hybrid nanospheres. Protective effect of chitosan nanospheres on indocyanine green molecules against hydrolysis and the body distribution of the CS-AuNR-ICG hybrid nanospheres are investigated. We focus on the synergic effect of gold nanorods and indocyanine green. This multifunctional material provides a model that has the functions of thermo/photodynamic therapy triggered by single near-infrared light radiation.(3) With peroxide oxalate ester, fluorescent dyes and photodynamic drug encapsuled in the micelles prepared from an amphiphilic block copolymer, multifunctional nanomicelles are prepared for imaging hydrogen peroxide. On one hand, nanomicelles can protect the peroxide oxalate ester from hydrolysis; on the other hand, the reaction energy of peroxide oxalate ester with hydrogen peroxide can be effectively transferred to adjacent fluorescent dye. The excited dye release chemiluminescence for photodynamic treatment, combining the diagnosis and therapy of tumor. Since the photodynamic therapy can be inspired by endogenous chemiluminescence, tumor treatment can be achieved regardless of depth of the tumor. This provides a solution to the problem of photodynamic therapy which cannot treat deep tumor in the body.