UCLA

Drug delivery techniques have been intensely explored to optimize the administration of therapeutics. Drug delivery formulations and devices are developed to improve the pharmacological property and therapeutic performance of drugs by altering the pharmacokinetics. Stimuli-responsive drug delivery systems have been constructed to achieve spatial and temporal control of drug release. With advanced chemistry and materials science, stimuli-responsive systems are demonstrated in response to different endogenous cues or exogenous signals. To control release profiles and reduce “off-target” release, exogenous stimuli are introduced to trigger drug release in a non-invasive manner. In recent years, cancer immunotherapy has become a powerful strategy for cancer treatment, and a variety of drug delivery techniques have been presented to enhance the therapeutic effects of immunotherapy. This thesis aims at designing and fabricating novel drug delivery formulations and devices to achieve photoactivated drug delivery and boost cancer immunotherapy. We first summarize the current techniques of stimuli-responsive drug delivery. Near infrared (NIR) light is a good candidate to trigger drug release in deep tissues, but the NIR-responsive materials are still limited as a drug loading carrier. We also review the barriers of immunotherapy against solid tumors and demonstrate a variety of delivery techniques to overcome these barriers. Among them, local hyperthermia as a combinational treatment can enhance the efficacy of immunotherapy. We construct a photoactivated drug delivery system based on a novel π-stacked organic framework (πOF). It demonstrates an intrinsic absorption of NIR light and superior photothermal effect. πOF not only has considerable loading capacity (more than 36 %) for a variety of drugs, but also prompts the inducible burst release of loaded cargoes under NIR irradiation with a ten-fold increase of the release rate. Based on these features, πOF is utilized to effectively modulate the delivery of resiquimod (R848) and simultaneously induce photothermal effect by NIR irradiation. The πOF-based drug delivery system is utilized to boost cancer immunotherapy. The R848/πOF complex is encapsulated in a polymeric microneedle patch for transdermal drug delivery. R848 is released from the system by photoactivation, which polarizes macrophages into tumor-destructive M1 phenotypes. The phagocytosis of macrophages is enhanced, together with the augment of proinflammatory cytokine secretion. In the 4T1 murine breast tumor model, the photoactivated release of R848 facilitates cancer immunotherapy by promoting the polarization and phagocytotic activity of macrophages. We design and fabricate a thin-film wireless heating device for magnetic hyperthermia treatments. Biodegradable metals and polymers are adopted to build the implantable device, so it can gradually dissolve in physiological environments. The device structure is designed as a coil antenna, which receives power from alternating magnetic field of radio frequency. We demonstrate that the device can increase its surface temperature to 70 ℃ in air and heat up water to 45 ℃. Considering the beneficial effects of hyperthermia on cancer immunotherapy, the wireless heating device is expected to treat solid tumors as a wireless on-demand therapeutic system.