TY - JOUR
T1 - Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles
AU - Rijcken, Cristianne J. F.
AU - de Lorenzi, Federica
AU - Biancacci, Ilaria
AU - Hanssen, Rob G. J. M.
AU - Thewissen, Marielle
AU - Hu, Qizhi
AU - Atrafi, Florence
AU - Liskamp, Rob M. J.
AU - Mathijssen, Ron H. J.
AU - Miedema, Iris H. C.
AU - Menke - van der Houven van Oordt, C. Willemien
AU - van Dongen, Guus A. M. S.
AU - Vugts, Danielle J.
AU - Timmers, Matt
AU - Hennink, Wim E.
AU - Lammers, Twan
N1 - Funding Information: CJFR, RH, MTh, QH and MTi are employees of Cristal Therapeutics. The other authors have no competing interest to disclose. The authors gratefully acknowledge financial support by the European Research Council (TL – ERC Consolidator Grant 864121: Meta-Targeting), the European Fund for Regional Development (FDL, TL – TAKTIRA: Project number: EFRE-0801767)), the German Research Foundation (IB, TL – DFG: GRK2375 (Project number: 331065168) and SFB1066), Horizon SME grant (784127), and the German Federal Ministry of Research and Education (TL; BMBF: Gezielter Wirkstofftransport, PP-TNBC, Project number 16GW0319K). Publisher Copyright: © 2022 Elsevier B.V.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec® technology is based on amphiphilic methoxy-poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG-b-pHPMAmLacn) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM). Key features of CCPM are a prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in the majority of healthy tissues. Proprietary hydrolysable linkers allow for tunable and sustained release of entrapped API, including hydrophobic and hydrophilic small molecules, as well as peptides and oligonucleotides. Preclinical imaging experiments provided valuable information on their tumor and tissue accumulation and distribution, as well as on uptake by cancer, healthy and immune cells. The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models. In the clinic, CPC634 also demonstrated favorable pharmacokinetics, good tolerability, signs of efficacy, and enhanced localization in tumor tissue as compared to conventional docetaxel. PET imaging of radiolabeled CPC634 showed quantifiable accumulation in ∼50 % of tumors and metastases in advanced-stage cancer patients, and demonstrated potential for use in a theranostic setting even when applied at a companion diagnostic dose. Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG-b-pHPMAmLacn CCPM based on CriPec® technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy.
AB - Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec® technology is based on amphiphilic methoxy-poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG-b-pHPMAmLacn) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM). Key features of CCPM are a prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in the majority of healthy tissues. Proprietary hydrolysable linkers allow for tunable and sustained release of entrapped API, including hydrophobic and hydrophilic small molecules, as well as peptides and oligonucleotides. Preclinical imaging experiments provided valuable information on their tumor and tissue accumulation and distribution, as well as on uptake by cancer, healthy and immune cells. The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models. In the clinic, CPC634 also demonstrated favorable pharmacokinetics, good tolerability, signs of efficacy, and enhanced localization in tumor tissue as compared to conventional docetaxel. PET imaging of radiolabeled CPC634 showed quantifiable accumulation in ∼50 % of tumors and metastases in advanced-stage cancer patients, and demonstrated potential for use in a theranostic setting even when applied at a companion diagnostic dose. Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG-b-pHPMAmLacn CCPM based on CriPec® technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy.
KW - Drug targeting
KW - Imaging
KW - Nanomedicine
KW - Polymeric micelles
KW - Theranostics
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85141467959&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36343757
U2 - https://doi.org/10.1016/j.addr.2022.114613
DO - https://doi.org/10.1016/j.addr.2022.114613
M3 - Review article
C2 - 36343757
SN - 0169-409X
VL - 191
JO - Advanced drug delivery reviews
JF - Advanced drug delivery reviews
M1 - 114613
ER -