Loading...
1 results
Search Results
Now showing 1 - 1 of 1
- Development and characterization of PLGA- Gold nanocapsules for combinatorial therapy of cancerPublication . Borges, Soraia dos Santos; Moreira, André Ferreira; Correia, Ilídio Joaquim Sobreira; Fernandes, Natanael Filipe FerreiraCancer constitutes a major public health issue and is the second cause of death worldwide. Currently, conventional treatments like radiation and chemotherapy encounter serious drawbacks and cannot, often, provide satisfactory outcomes, mainly due to the limited therapeutic efficacy and considerable side effects. Given these limitations, the development of new and more effective cancer treatments, such as immunotherapy, gene therapy, and hyperthermia, has attracted much attention from the scientific and medical communities. Hyperthermia is a promising approach to improve cancer treatment, and its combination with nanotechnology has been explored to create more specific and effective therapeutic modalities, such as photothermal therapy (PTT). The PTT mediated by nanoparticles leverages the capacity of certain nanomaterials to convert light into heat, creating a localized temperature increase. This event can then be harnessed for therapeutic purposes by inducing the death of cancer cells or increasing their sensitivity to other therapeutic agents. Gold nanoparticles are one of many types of nanomaterials that can be explored to mediate a photothermal effect. Moreover, the gold nanoparticles can also be tailored for drug delivery and act as contrast agents in the conventionally used imaging techniques. Nevertheless, the innate therapeutic potential of gold nanoparticles is hindered by their high reactivity towards thiol groups and photodegradation events. The work plan of my Master’s dissertation aimed to develop and optimize the synthesis of PLGA/Gold nanocapsules with the capacity to act as photothermal agents and drug carriers in cancer therapy. The PLGA poly(lactic-co-glycolic acid) was selected due to its versatility and well-known biological compatibility, which have led to the approval of several PLGA-based drug delivery systems and medical devices for clinical application by the regulatory authorities. The production of the PLGA/Gold nanocapsules was achieved via a double emulsion methodology (water-in-oil-in-water (W/O/W) emulsion), where gold nanospheres with 19 nm were added to the first water phase. During this work, three different formulations were tested, formulation A (following a normal methodology for producing PLGA nanocapsules), formulation B (higher volume of the first water phase, i.e., higher amount of gold nanospheres), and formulation C (higher volume of the oil phase). All formulations presented a size of ˜350 nm and a negative surface charge (i.e., -24.9, -19.9, and –11.7 mV for formulations A, B, and C, respectively). Moreover, upon NIR laser irradiation, the PLGA/Gold nanocapsules mediated an increase in the temperature of 11.7ºC (Formulation A), 9.3ºC (Formulation B), and 10.2ºC (Formulation C). This photothermal capacity was further confirmed by Scanning Electron Microscopy (SEM) microscopy with the destruction of the polymeric nanocapsules. Additionally, the preliminary results for the Encapsulation Efficiency (E.E.) show that only ˜50% AO is encapsulated in the PLGA/Gold nanocapsules, demonstrating the capacity to act as a drug carrier. In turn, preliminary cell studies showed that all the formulations are biocompatible both with healthy (fibroblasts) and carcinogenic (cervical cancer) cells, even at concentrations of 400 µg/mL. Furthermore, assays performed in the HeLa cells showed that the combination of the photothermal effect and AO delivery results in an antitumoral effect, reducing the viability of HeLa cells to less than 60%. In summary, the present findings confirm the potential of these PLGA/Gold nanocapsules for being applied in cancer therapy. Nevertheless, in the future, the therapeutic potential of PLGA/Gold nanocapsules will also be evaluated in more complex in vitro models, namely on tumor spheroids, characterizing both the uptake and the cytotoxic capacity. Moreover, according to the data obtained from these assays, the reengineering of the PLGA/Gold nanocapsules can also be considered namely the optimization of the photothermal effect and drug encapsulation efficiency.