| Resumo: |
Rectal cancer (RC) accounts for 30% of colorectal cancer cases, the second most common cause of cancer-related deaths in Europe. In many cases RC is resistant or develop resistance toionizing radiation, which narrows therapeutic options. Alternative treatments, such as photothermal therapy (PTT),and photodynamic therapy (PDT) based on nanoparticle systems have been proposed, but these still require improvements, namely in terms of control over selective heating and localized production of reactive oxygen species(ROS) on tumor cells/area, or enhancement of drug loading capacity and fine control over tumor-targeted drug release. The design of multifunctional nanomedicines that could be used for synergistic combination of PTT/PDT/chemotherapy treatmentsis still a new challenging field. Biocompatibility of mostcurrently available nanoparticles is still debatable, further pressing the need for exploration of alternative materials. This demands the finding of alternative delivery strategies for both anti-cancer agents and phototherapy. PhotoRect intends to develop new pharmaceutical formulations for phototherapy of RC treatment using innovative nanomaterials and drugs. The large surface area and radiation absorbance properties of innovative nanomaterials, place them as ideal platforms for the design of multifunctional nanomedicines. One of the main issues slowing the clinical translation of innovativenanomaterials, is their limited availability and production reproducibility, due to production methods being complex and having low yield. However, our team has optimized innovative nanomaterials production methods and successfully scaled up batch sizes, assuring the availability of materials withappropriate properties, guaranteeing water dispersion stability, increased tissue penetration and retention within the tumor, and improving their biocompatibility. Through this work, we will be able to better understand how innovative nanomaterials act in aqueous environments and  |
Resumo
Rectal cancer (RC) accounts for 30% of colorectal cancer cases, the second most common cause of cancer-related deaths in Europe. In many cases RC is resistant or develop resistance toionizing radiation, which narrows therapeutic options. Alternative treatments, such as photothermal therapy (PTT),and photodynamic therapy (PDT) based on nanoparticle systems have been proposed, but these still require improvements, namely in terms of control over selective heating and localized production of reactive oxygen species(ROS) on tumor cells/area, or enhancement of drug loading capacity and fine control over tumor-targeted drug release. The design of multifunctional nanomedicines that could be used for synergistic combination of PTT/PDT/chemotherapy treatmentsis still a new challenging field. Biocompatibility of mostcurrently available nanoparticles is still debatable, further pressing the need for exploration of alternative materials. This demands the finding of alternative delivery strategies for both anti-cancer agents and phototherapy. PhotoRect intends to develop new pharmaceutical formulations for phototherapy of RC treatment using innovative nanomaterials and drugs. The large surface area and radiation absorbance properties of innovative nanomaterials, place them as ideal platforms for the design of multifunctional nanomedicines. One of the main issues slowing the clinical translation of innovativenanomaterials, is their limited availability and production reproducibility, due to production methods being complex and having low yield. However, our team has optimized innovative nanomaterials production methods and successfully scaled up batch sizes, assuring the availability of materials withappropriate properties, guaranteeing water dispersion stability, increased tissue penetration and retention within the tumor, and improving their biocompatibility. Through this work, we will be able to better understand how innovative nanomaterials act in aqueous environments and if their properties can be tuned for phototherapy uses. Furthermore, innovative nanomaterials/drug conjugates physicochemical, drug loading and release, and biological characterization methods are implemented. This project will allow testing of different state-of-the-art cancer treatment strategies and searching innovative nanomaterials to enable multifunctional designs. The in vitro and in vivo anti-cancer effects of those innovative nanomaterials combined with PTT, PDT will be studied at i3S, by a team of biomedical researchers specialized in pharmacy and cancer treatment, as well as in innovative nanomaterials bioactivity evaluation. Furthermore, FEUP and UT Austin teams are already collaborating and preparing innovative nanomaterials together. Also, between i3S and FEUP a collaboration with more than 12 years is in place for innovative nanomaterials study for healthcare applications.
Currently, it is not possible to find most of those innovative nanomaterials available commercially that have the propertiesneeded for this application, which maximize biological stability and effect. It is expected that biological uses even beyond theproposed approaches are found. Also, innovative nanomaterials can be provided to other institutions and applications might befound in diverse fields. All platforms optimized, will provide cancer treatment option easily implementable anywhere in the globe (UN2030 - Goal 3).
All effective results will be patented, further studied in vivo, and translation to clinics and industry will be pursued. |