A sulfobetaine zwitterionic polymer-drug conjugate for multivalent paclitaxel and gemcitabine co-delivery

Haotian Sun; Lingyue Yan; Runsheng Zhang; Jonathan F. Lovell; Yun Wu; Chong Cheng

doi:10.1039/d1bm00393c

A sulfobetaine zwitterionic polymer-drug conjugate for multivalent paclitaxel and gemcitabine co-delivery

Haotian Sun
, Lingyue Yan
, Runsheng Zhang
, Jonathan F. Lovell
, Yun Wu
, Chong Cheng

SUNY Buffalo

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

A zwitterionic polymer-drug conjugate (ZPDC) strategy is developed for the co-delivery of paclitaxel (PTX) and gemcitabine (GEM) chemotherapeutics, as well as a near-infrared fluorescence imaging agent cyanine5.5 (Cy5.5). The well-defined ZPDC is synthesized by tandem azide-Alkyne and thiol-ene click functionalization of a biodegradable acetylenyl/allyl-functionalized polylactide and zwitterionic character is conferred by sulfobetaine. It has a number-Average molecular weight of 53.6 kDa, comprising 6.5% PTX and 17.7% GEM by weight. Cy5.5 moieties are readily introduced to the ZPDC via conjugation. In aqueous solutions, the ZPDC exhibits a hydrodynamic diameter of 46 nm. In vitro MIA PaCa-2 human pancreatic cancer cells show strong ZPDC cellular uptake and cytotoxicity. In mice, the ZPDC exhibits long blood circulation, effective tumor accumulation, biocompatibility, therapeutic effect, and integrated imaging capacity. Overall, this work illustrates that ZPDCs are promising systems for chemotherapy delivery and bioimaging applications.

Original language	English
Pages (from-to)	5000-5010
Number of pages	11
Journal	Biomaterials Science
Volume	9
Issue number	14
DOIs	https://doi.org/10.1039/d1bm00393c
State	Published - Jul 21 2021

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title = "A sulfobetaine zwitterionic polymer-drug conjugate for multivalent paclitaxel and gemcitabine co-delivery",

abstract = "A zwitterionic polymer-drug conjugate (ZPDC) strategy is developed for the co-delivery of paclitaxel (PTX) and gemcitabine (GEM) chemotherapeutics, as well as a near-infrared fluorescence imaging agent cyanine5.5 (Cy5.5). The well-defined ZPDC is synthesized by tandem azide-Alkyne and thiol-ene click functionalization of a biodegradable acetylenyl/allyl-functionalized polylactide and zwitterionic character is conferred by sulfobetaine. It has a number-Average molecular weight of 53.6 kDa, comprising 6.5\% PTX and 17.7\% GEM by weight. Cy5.5 moieties are readily introduced to the ZPDC via conjugation. In aqueous solutions, the ZPDC exhibits a hydrodynamic diameter of 46 nm. In vitro MIA PaCa-2 human pancreatic cancer cells show strong ZPDC cellular uptake and cytotoxicity. In mice, the ZPDC exhibits long blood circulation, effective tumor accumulation, biocompatibility, therapeutic effect, and integrated imaging capacity. Overall, this work illustrates that ZPDCs are promising systems for chemotherapy delivery and bioimaging applications.",

author = "Haotian Sun and Lingyue Yan and Runsheng Zhang and Lovell, \{Jonathan F.\} and Yun Wu and Chong Cheng",

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T1 - A sulfobetaine zwitterionic polymer-drug conjugate for multivalent paclitaxel and gemcitabine co-delivery

AU - Sun, Haotian

AU - Yan, Lingyue

AU - Zhang, Runsheng

AU - Lovell, Jonathan F.

AU - Wu, Yun

AU - Cheng, Chong

N1 - Publisher Copyright: © The Royal Society of Chemistry.

PY - 2021/7/21

Y1 - 2021/7/21

N2 - A zwitterionic polymer-drug conjugate (ZPDC) strategy is developed for the co-delivery of paclitaxel (PTX) and gemcitabine (GEM) chemotherapeutics, as well as a near-infrared fluorescence imaging agent cyanine5.5 (Cy5.5). The well-defined ZPDC is synthesized by tandem azide-Alkyne and thiol-ene click functionalization of a biodegradable acetylenyl/allyl-functionalized polylactide and zwitterionic character is conferred by sulfobetaine. It has a number-Average molecular weight of 53.6 kDa, comprising 6.5% PTX and 17.7% GEM by weight. Cy5.5 moieties are readily introduced to the ZPDC via conjugation. In aqueous solutions, the ZPDC exhibits a hydrodynamic diameter of 46 nm. In vitro MIA PaCa-2 human pancreatic cancer cells show strong ZPDC cellular uptake and cytotoxicity. In mice, the ZPDC exhibits long blood circulation, effective tumor accumulation, biocompatibility, therapeutic effect, and integrated imaging capacity. Overall, this work illustrates that ZPDCs are promising systems for chemotherapy delivery and bioimaging applications.

AB - A zwitterionic polymer-drug conjugate (ZPDC) strategy is developed for the co-delivery of paclitaxel (PTX) and gemcitabine (GEM) chemotherapeutics, as well as a near-infrared fluorescence imaging agent cyanine5.5 (Cy5.5). The well-defined ZPDC is synthesized by tandem azide-Alkyne and thiol-ene click functionalization of a biodegradable acetylenyl/allyl-functionalized polylactide and zwitterionic character is conferred by sulfobetaine. It has a number-Average molecular weight of 53.6 kDa, comprising 6.5% PTX and 17.7% GEM by weight. Cy5.5 moieties are readily introduced to the ZPDC via conjugation. In aqueous solutions, the ZPDC exhibits a hydrodynamic diameter of 46 nm. In vitro MIA PaCa-2 human pancreatic cancer cells show strong ZPDC cellular uptake and cytotoxicity. In mice, the ZPDC exhibits long blood circulation, effective tumor accumulation, biocompatibility, therapeutic effect, and integrated imaging capacity. Overall, this work illustrates that ZPDCs are promising systems for chemotherapy delivery and bioimaging applications.

UR - https://www.scopus.com/pages/publications/85110262517

U2 - 10.1039/d1bm00393c

DO - 10.1039/d1bm00393c

M3 - Article

C2 - 34105535

AN - SCOPUS:85110262517

SN - 2047-4830

VL - 9

SP - 5000

EP - 5010

JO - Biomaterials Science

JF - Biomaterials Science

IS - 14

ER -

A sulfobetaine zwitterionic polymer-drug conjugate for multivalent paclitaxel and gemcitabine co-delivery

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