ENGINEERING MAGNETIC DEVICE AND NANOPARTICLES PLATFORMS TO IMPROVE DRUG ACCUMULATION AND PENETRATION IN TUMORS FOR ENHANCED CANCER TREATMENT

Drug delivery strategies aim to maximize the accumulation of therapeutic agents at targeted sites, such as tumors, while minimizing off-target delivery to healthy tissues, thereby enhancing therapeutic efficacy and reducing unwanted side effects. Nanoparticles have garnered significant interest as drug delivery vehicles for cancer treatment, yet they frequently suffer from physical and biological obstacles during systemic administration. These challenges include, but are not limited to, the complex biological structures within the tumor microenvironment, which impedes the effective accumulation and penetration of nanocarriers into target tumors. Among various external stimulus strategies, magnetic fields induced by single external static magnets have been employed to improve the delivery of magnetic nanocarriers to tumors. However, their effectiveness is limited to superficial tumors due to the rapid decline in magnetic field strength with distance from the magnet. To overcome the limitations of using a single magnet, a 2−magnet device was developed to enhance the targeting of magnetic nanocarriers to greater tissue depths, leveraging the constant magnetic field gradient created between two oppositely polarized magnets. Despite these advancements, there was still room for improvement. This study further advances the technology by constructing an 8−magnet device arranged in an annular Halbach array. This configuration promotes radial outward movement of nanoparticles from the center of the bore due to its enhanced constant magnetic gradient. By utilizing Chlorin e6-coated magnetic nanoclusters (Ce6 clusters) with densely packed cobalt-doped superparamagnetic iron oxide nanoparticles for improved magnetic responsiveness, a nearly 3.7-fold increase in tumor accumulation and a 3.5-fold improvement in intra-tumoral penetration were achieved compared to the 2−magnet device. This advancement significantly enhanced the efficacy of photodynamic therapy and chemotherapy, showcasing the potential therapeutic applications of this approach.

Author dc:creator

• Jang, Bian

Advisor dc:contributor.advisor

• Tsourkas, Andrew

• Engineering

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/60865

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/60865