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Multi-Functional Nanogels as Theranostic Platforms: Exploiting Reversible and Nonreversible Linkages for Targeting, Imaging, and Drug Delivery.
Bioconjug Chem. 2018 06 20; 29(6):1885-1896.BC

Abstract

Nanogels that are amenable to facile multi-functionalization with imaging, therapeutic, and targeting agents are attractive theranostic platforms for addressing challenges in conventional diagnostics and therapy. In this work, reactive copolymers containing poly(ethylene glycol), maleimide, and pendant hydroxyl groups as side chains are used to construct nanogels by employing their thermoresponsive self-assembly in aqueous media. Subsequent cross-linking of these nanosized aggregates with dithiols using thiol-maleimide chemistry yields nanogels containing maleimide, thiol, and hydroxyl groups. The hydroxyl groups are readily activated to N-hydroxysuccinimide based carbonates that undergo conjugation with amine-containing molecules through carbamate linkage under mild conditions. As a demonstration of multi-functionalization, the maleimide, thiol, and activated carbonate groups were functionalized with a thiol-containing cancer cell targeting peptide, a maleimide-containing fluorescent indocyanine Cy5 dye, and an anticancer drug doxorubicin, respectively. It was observed that enhanced drug release from nanogels occurs under acidic conditions. While the parent nanogel vehicles did not possess any toxicity, drug conjugated constructs with and without targeting group were cytotoxic against MDA-MB-231 breast cancer cells. The cyclic peptide containing targeted nanogel exhibited slightly higher cytotoxicity than its counterpart devoid of any targeting group. Furthermore, higher level of drug internalization into MDA-MB-231 cells was observed for the targeting group containing construct. It can be envisioned that facile fabrication and multi-functionalization of these reactive nanogels simultaneously through nonreversible and reversible linkages offers a modular platform that can be configured as a theranostic agent for addressing challenges in conventional therapy of various diseases.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29727179

Citation

Chambre, Laura, et al. "Multi-Functional Nanogels as Theranostic Platforms: Exploiting Reversible and Nonreversible Linkages for Targeting, Imaging, and Drug Delivery." Bioconjugate Chemistry, vol. 29, no. 6, 2018, pp. 1885-1896.
Chambre L, Degirmenci A, Sanyal R, et al. Multi-Functional Nanogels as Theranostic Platforms: Exploiting Reversible and Nonreversible Linkages for Targeting, Imaging, and Drug Delivery. Bioconjug Chem. 2018;29(6):1885-1896.
Chambre, L., Degirmenci, A., Sanyal, R., & Sanyal, A. (2018). Multi-Functional Nanogels as Theranostic Platforms: Exploiting Reversible and Nonreversible Linkages for Targeting, Imaging, and Drug Delivery. Bioconjugate Chemistry, 29(6), 1885-1896. https://doi.org/10.1021/acs.bioconjchem.8b00085
Chambre L, et al. Multi-Functional Nanogels as Theranostic Platforms: Exploiting Reversible and Nonreversible Linkages for Targeting, Imaging, and Drug Delivery. Bioconjug Chem. 2018 06 20;29(6):1885-1896. PubMed PMID: 29727179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multi-Functional Nanogels as Theranostic Platforms: Exploiting Reversible and Nonreversible Linkages for Targeting, Imaging, and Drug Delivery. AU - Chambre,Laura, AU - Degirmenci,Aysun, AU - Sanyal,Rana, AU - Sanyal,Amitav, Y1 - 2018/05/24/ PY - 2018/5/5/pubmed PY - 2019/4/16/medline PY - 2018/5/5/entrez SP - 1885 EP - 1896 JF - Bioconjugate chemistry JO - Bioconjug. Chem. VL - 29 IS - 6 N2 - Nanogels that are amenable to facile multi-functionalization with imaging, therapeutic, and targeting agents are attractive theranostic platforms for addressing challenges in conventional diagnostics and therapy. In this work, reactive copolymers containing poly(ethylene glycol), maleimide, and pendant hydroxyl groups as side chains are used to construct nanogels by employing their thermoresponsive self-assembly in aqueous media. Subsequent cross-linking of these nanosized aggregates with dithiols using thiol-maleimide chemistry yields nanogels containing maleimide, thiol, and hydroxyl groups. The hydroxyl groups are readily activated to N-hydroxysuccinimide based carbonates that undergo conjugation with amine-containing molecules through carbamate linkage under mild conditions. As a demonstration of multi-functionalization, the maleimide, thiol, and activated carbonate groups were functionalized with a thiol-containing cancer cell targeting peptide, a maleimide-containing fluorescent indocyanine Cy5 dye, and an anticancer drug doxorubicin, respectively. It was observed that enhanced drug release from nanogels occurs under acidic conditions. While the parent nanogel vehicles did not possess any toxicity, drug conjugated constructs with and without targeting group were cytotoxic against MDA-MB-231 breast cancer cells. The cyclic peptide containing targeted nanogel exhibited slightly higher cytotoxicity than its counterpart devoid of any targeting group. Furthermore, higher level of drug internalization into MDA-MB-231 cells was observed for the targeting group containing construct. It can be envisioned that facile fabrication and multi-functionalization of these reactive nanogels simultaneously through nonreversible and reversible linkages offers a modular platform that can be configured as a theranostic agent for addressing challenges in conventional therapy of various diseases. SN - 1520-4812 UR - https://www.unboundmedicine.com/medline/citation/29727179/Multi_Functional_Nanogels_as_Theranostic_Platforms:_Exploiting_Reversible_and_Nonreversible_Linkages_for_Targeting_Imaging_and_Drug_Delivery_ L2 - https://dx.doi.org/10.1021/acs.bioconjchem.8b00085 DB - PRIME DP - Unbound Medicine ER -