Development of an injectable dual drug nanocarriers-loaded alginate composite hydrogel for photochemotherapy of breast cancer (1/2)

[1] Specific Aim: We aim to design and fabricate multifunctional alginate composite hydrogel containing indocyanine green (ICG)-encapsulated perfluorocarbon (PFC) nanoemulsions (IPNEs) and camptothecin (CPT)-loaded chitosan nanoparticles (CCNPs) named IPECNPAHG, and explore its potential on photochemotherapy of breast cancer. [2] Background: Hydrogel has been demonstrated as an emerging and promising therapeutic strategy for cancer treatment. CPT is one of the most commonly used anticancer drugs with USFDA approval. However, serious side effects due to use of high dosage is always the concern for all the anticancer drugs. ICG, a watersoluble tricarbocyanine dye, is one of few clinically proved NIR photosensitizer and has been extensively used in cancerous phototherapy since it can produce hyperthermia and singlet oxygen upon NIR irradiation. However, drawbacks of ICG such as poor stability and limited oxygen content in tissues tremendously hinder its applicability in the clinic. To overcome the aforementioned challenges, we aim to develop the IPECNPAHG through use of oxyphilic perfluorocarboncombined with nanotechnology, and anticipate that such an emerging material is highly applicable for use in cancer treatment. [3] Advantages: The developed IPECNPAHG may provide following advantages as used in the clinic: 1) Both ICG and CPT can be concurrently brought to the tumor site through use of the IPECNPAHG to improve the anticancer efficacy. 2) The IPECNPAHG may provide both physical (photothermal and photodynamic therapies) and chemical (chemotherapy) approaches to eradicate cancer cells and thereby the tumoricidal effectiveness can be greatly enhanced. 3) Since perfluorocarbon possesses high O2-dissolving capability, the developed IPECNPAHG is foreseeably able to provide an enhanced effect of photodynamic therapy. 4) Both ICG and CPT can be protected by the nanocarriers and hydrogel by which the stability of drug particularly ICG can be dramatically enhanced. Furthermore, since the IPECNPAHG can offer adjuvant phototherapy, the effective dose of CPT provided by the composite hydrogel is theoretically lower than that performed by CPT alone and thereby the level of chemotherapyinduced side effects on patients can be reduced. [4] Qualification/Capability: The project PI (YH Lee) has long research background in the fields of nanomedicine and biomaterials, and has practical hands-on experience on design and manufacture of nano-drug carriers and hydrogel dressings in the past 5 years. The partner company; Yu Green Co. Ltd., is a well-established chemical/bio-tech company with robust expertise/professions in fundamental material sciences, applications of anticancer biomaterials, and instrumental analysis. Therefore, such partnership is perfectly qualified to conduct this industry-academia collaboration project. [5] Research Schedule: The overall task in this IPECNPAHG study can be divided into four stages. In this current project, we will finish 1) the 1st stage “To fabricate, characterize and optimize the IIPECNPAHG” (1 - 7 Month) and 2) the 2nd stage “To assess the anticancer capability and dose efficacy of the IPECNPAHG through an in vitro cell assay” (8 - 12 Month).