The response to current therapies for metastatic castration resistant prostate cancer (mCRPC) has been highly heterogenous. This necessitates precision medicine and improved diagnostic tests for patient stratification to enhance therapeutic response. Identification of novel targets such as PSMA and PARP along with the subsequent FDA approval of their respective targeted drugs such as Pluvicto^Ò and Talzenna^Ò represents a leap in precision medicine. However, tumor targeted delivery of targeted drugs is essential to improve survival and avoid primary or acquired resistance.

Large-size nanocarriers are known to accumulate in the tumor, allowing for targeted delivery of drugs mediated by the enhanced permeability and retention (EPR) effect. Specific targeting of nanocarriers has potential to improve imaging contrast and therapeutic effect. We have designed and synthesized novel prostate cancer specific Star-PEG_40kDa nanocarriers using PSMA-targeting ACUPA with ⁸⁹Zr and ¹⁷⁷Lu radiolabeling for selective tumor delivery.

Figure: PSMA-targeted ACUPA ligand specific Star-PEG_40kDa nanocarriers for microSPECT/CT imaging using 177Lu-labeled nanocarriers. As we utilize the multivalent targeting with high affinity ligands, high radiation doses can be selectively delivered to tumors for improved imaging contrast and enhanced therapeutic efficacy of prostate cancer.

For more information, refer to our published work:

1. Meher N, Ashley GW, Bobba KN, Wadhwa A, Bidkar AP, Dasari C, Mu C, Sankaranarayanan RA, Serrano JAC, Raveendran A, Bulkley DP, Aggarwal R, Greenland NY, Oskowitz A, Wilson DM, Seo Y, Santi DV, VanBrocklin HF, Flavell RR. Prostate-Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer. Adv Healthc Mater. 2024 May 3:e2304618. doi: 10.1002/adhm.202304618. Epub ahead of print. PMID: 38700450.
2. Meher N, Ashley GW, Bidkar AP, Dhrona S, Fong C, Fontaine SD, Beckford Vera DR, Wilson DM, Seo Y, Santi DV, VanBrocklin HF, Flavell RR. Prostate-Specific Membrane Antigen Targeted Deep Tumor Penetration of Polymer Nanocarriers. ACS Appl Mater Interfaces. 2022 Nov 16;14(45):50569-50582. doi: 10.1021/acsami.2c15095. Epub 2022 Nov 1. PMID: 36318757; PMCID: PMC9673064.
3. Meher N, VanBrocklin HF, Wilson DM, Flavell RR. PSMA-Targeted Nanotheranostics for Imaging and Radiotherapy of Prostate Cancer. Pharmaceuticals (Basel). 2023 Feb 17;16(2):315. doi: 10.3390/ph16020315. PMID: 37259457; PMCID: PMC9964110.