Targeted Drug Delivery Solutions for Advanced Prostate Cancer

Unmet Need: Highly Effective and Selective Drug Delivery Methods for Advanced-Stage Prostate Cancer Treatment

Prostate cancer is the second leading cause of cancer-related deaths among men in the United States, with advanced cases requiring urgent treatment. Current therapies offer only limited survival benefits, and many chemotherapies cause severe side effects due to their non-selective distribution, damaging healthy tissues. The five-year survival rate for patients with metastatic castration-resistant prostate cancer (mCRPC) remains low, around 30%. Treatment options are scarce, largely due to the difficulty in delivering drugs specifically to prostate cancer cells without harming healthy organs. Therefore, there is a critical need for advanced platforms that can selectively deliver potent chemotherapeutics to prostate cancer cells, minimizing side effects and improving patient outcomes.

The Technology: The technology is a novel dendrimer based systemic PSMA-targeted nano platform for prostate cancer-specific targeted drug delivery. The PSMA-D-Cabo technology is an exciting breakthrough in the targeted nanotherapy landscape for advanced prostate cancer, harnessing the unique characteristics of Prostate-Specific Membrane Antigen (PSMA), which is predominantly expressed in prostate cancer cells. This cutting-edge platform ingeniously integrates PAMAM-OH dendrimers (Clinical trials), an irreversible PSMA ligand (CTT1298- clinical trials as a diagnostic agent for prostate cancer), and the potent chemotherapeutic cabozantinib (Approved for HCC & RCC) into a synergistic solution designed to combat mCRPC. By leveraging the multivalent nature of dendrimers, PSMA-D-Cabo ensures precise and selective delivery of cabozantinib directly to PSMA-positive tumor cells while minimizing off-target effects, a significant challenge in conventional therapies. Preclinical studies have demonstrated that PSMA-D-Cabo markedly enhances the anti-proliferative efficacy of cabozantinib compared to its free form, coupled with favorable pharmacokinetics, including rapid clearance from non-target tissues through kidneys.

Designed for convenient intravenous administration, this innovative technology not only improves the stability and solubility of hydrophobic cabozantinib but also holds the promise of transforming treatment paradigms in advanced prostate cancer. With its components showing established clinical success, PSMA-D-Cabo stands poised to redefine patient outcomes, offering hope for more effective therapies with reduced side effects. In-Vivo efficacy evaluation is going on in clinically relevant patient-derived xenograft (PDX) models of Prostate Cancer.

Applications:

• Targeted Treatment: PSMA-D-Cabo facilitates precise delivery of cabozantinib directly to PSMA-positive tumors, enhancing therapeutic efficacy in metastatic castration-resistant prostate cancer (mCRPC). The platform retains in the tumor and clears rapidly from the rest of the body through kidneys.
• Diverse platform for targeted delivery: Can deliver a range of chemotherapeutic agents beyond cabozantinib
• Combination Therapy Potential: The technology's multivalent dendrimer structure allows for simultaneous delivery of multiple therapeutic agents, paving the way for synergistic treatment approaches. This dendrimer technology can synergistically deliver chemotherapy along with radioligand therapy.

Advantages:

• Pluvicto's recent approval validates the clinical relevance of targeting PSMA in prostate cancer treatment. This establishes a market precedent for PSMA-based therapies, enhancing the credibility and attractiveness of PSMA-D-Cabo.
• Enhanced cellular uptake, PSMA-D-Cabo improve internalization rates of cabozantinib in and in turn efficacy in target cells.
• Increased target specificity
• Reduced systemic side effects
• Flexible platform for combination therapy for advanced prostate cancer treatment

Patent & Manuscript Information:

Provisional patent application has been filed.

Link for published papers; https://doi.org/10.1039/D3NR06520K

https://pubs.acs.org/doi/10.1021/acs.biomac.4c00878