Treatment of patients with lung cancer is a major clinical challenge where patients face an extremely poor prognosis. The poor response to standard systemic routes of administration of a drug is due to complex factors which include low therapeutic index of chemotherapeutics and physiological barriers to drug penetration into tumors. Among the cutting edge targeted cancer therapies, nanoparticle (NP) drug carrier systems have demonstrated enhanced permeability with successful drug delivery. The development of multifunctional Advanced Therapeutic Platforms (ATP) have the potential to effectively increase the therapeutic index for drugs by increasing local drug concentrations at the tumor site while minimizing the exposure to normal tissue. In addition, the ATP can be used as a cancer monitoring agent by encapsulating MRI contrast agents with the core of the ATP. The treatment of cancer using a targeted-ATP for delivery of a chemotherapeutic agent and a radiation sensitizer offers an attractive opportunity to overcome the obstacles that limit standard combined treatment approaches. Gemcitabine is a potent radiosensitizer whose clinical utility is limited by its inherent toxicity to normal tissues and short plasma half-life. The encapsulation of such drugs, thereby invading side effects, will have a major impact in clinical industry. The purpose is to engineer and validate a multifunctional ATP comprised of biocompatible and biodegradable ingredients that carries a payload of therapeutic drug(s), an imaging agent and a targeting tumor homing F3 peptide. The specific objective of this contract proposal is to develop a novel ATP for the targeted delivery of Gemcitabine to lung cancers while simultaneously monitoring the efficacy by MR imaging.
