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

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

doi:10.1039/d1bm00393c

Cited by 19 publications

(19 citation statements)

References 64 publications

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“…[83][84][85] Alternatively, zwitterionic materials such as poly (sulfobetaine), poly(carboxybetaine), and phosphorylcholinebased polymers (e.g., 2-methacryloyloxyethyl phosphorylcholine) are also able to improve nanoparticles' circulation time. [86][87][88][89] One of the interests of zwitterionic polymers over hydrophilic polymers is its stimuli-responsive capacity that offers a powerful strategy for delivering and releasing cargos at the desirable site and time. [90] Zwitterionic polymers confer high stability and hydration to nanoparticles' surfaces, which strongly reduce protein adsorption, compared with PEGylated nanoparticles.…”

Section: Surface Functionalization To Modulate the Nano-bio Interactionsmentioning

confidence: 99%

Cell‐Derived Vesicles for Nanoparticles' Coating: Biomimetic Approaches for Enhanced Blood Circulation and Cancer Therapy

Rodrigues

Fernandes

Melo‐Diogo

et al. 2022

Adv Healthcare Materials

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Cancer nanomedicines are designed to encapsulate different therapeutic agents, prevent their premature release, and deliver them specifically to cancer cells, due to their ability to preferentially accumulate in tumor tissue. However, after intravenous administration, nanoparticles immediately interact with biological components that facilitate their recognition by the immune system, being rapidly removed from circulation. Reports show that less than 1% of the administered nanoparticles effectively reach the tumor site. This suboptimal pharmacokinetic profile is pointed out as one of the main factors for the nanoparticles' suboptimal therapeutic effectiveness and poor translation to the clinic. Therefore, an extended blood circulation time may be crucial to increase the nanoparticles' chances of being accumulated in the tumor and promote a site‐specific delivery of therapeutic agents. For that purpose, the understanding of the forces that govern the nanoparticles' interaction with biological components and the impact of the physicochemical properties on the in vivo fate will allow the development of novel and more effective nanomedicines. Therefore, in this review, the nano–bio interactions are summarized. Moreover, the application of cell‐derived vesicles for extending the blood circulation time and tumor accumulation is reviewed, focusing on the advantages and shortcomings of each cell source.

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Section: Surface Functionalization To Modulate the Nano-bio Interactionsmentioning

confidence: 99%

Cell‐Derived Vesicles for Nanoparticles' Coating: Biomimetic Approaches for Enhanced Blood Circulation and Cancer Therapy

Rodrigues

Fernandes

Melo‐Diogo

et al. 2022

Adv Healthcare Materials

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“…18−22 However, these polymers with polyacrylate backbones do not possess biodegradability, which may result in bioaccumulation-related toxicity, hampering long-term applications. 23,24 Zwitterionic polypeptides possessing natural structures could be enzymatically digestible and metabolizable, exhibiting good biocompatibility and nontoxicity. 25,26 Nevertheless, synthesizing zwitterionic polypeptides requires precise control of the alternating sequence of amino acid units with opposite charges with the cumbersome process of protection and deprotection of free carboxyl and amino groups.…”

Section: Introductionmentioning

confidence: 99%

Robust Construction of Supersmall Zwitterionic Micelles Based on Hyperbranched Polycarbonates Mediates High Tumor Accumulation

Zhao

Wen

Pan

et al. 2023

ACS Appl. Mater. Interfaces

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Despite the numerous advantages of nanomedicines, their therapeutic efficacy is hampered by biological barriers, including fast in vivo clearance, poor tumor accumulation, inefficient penetration, and cellular uptake. Herein, cross-linked supersmall micelles based on zwitterionic hyperbranched polycarbonates can overcome these challenges for efficiently targeted drug delivery. Biodegradable acryloyl/zwitterion-functionalized hyperbranched polycarbonates are synthesized by a one-pot sequential reaction of Michael-type addition and ring-opening polymerization, followed by controlled modification with carboxybetaine thiol. Cross-linked supersmall zwitterionic micelles (X-CBMs) are readily prepared by straightforward self-assembly and UV cross-linking. X-CBMs exhibit prolonged blood circulation because of their cross-linked structure and zwitterion decoration, which resist protein corona formation and facilitate escaping RES recognition. Combined with the advantage of supersmall size (7.0 nm), X-CBMs mediate high tumor accumulation and deep penetration, which significantly enhance the targeted antitumor outcome against the 4T1 tumor model by administration of the paclitaxel (PTX) formulation (X-CBM@PTX).

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“…According to the particular characteristics of tumor microenvironment (such as low pH and high redox activity) and the aberrant biochemical properties of cancer cells, nanocarriers responsive to endogenous or exogenous stimuli have been designed and developed to enable site-specific control over the release of chemotherapeutics . For instance, we harnessed the pH-sensitivity of imine, acetal, and β-thiopropionate linkages to develop well-defined pH-responsive polylactide-based drug delivery systems with improved anticancer efficacy in our previous works. − However, the effective delivery of a single-component antitumor therapeutic agent may not sufficiently overcome the inherent limitations of chemotherapy, especially drug resistance of tumor cells …”

Section: Introductionmentioning

confidence: 99%

Well-Defined pH-Responsive Self-Assembled Block Copolymers for the Effective Codelivery of Doxorubicin and Antisense Oligonucleotide to Breast Cancer Cells

Mohamed

Yan

Shahini

et al. 2022

ACS Appl. Bio Mater.

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The worldwide steady increase in the number of cancer patients motivates the development of innovative drug delivery systems for combination therapy as an effective clinical modality for cancer treatment. Here, we explored a design concept based on poly(ethylene glycol)-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(2-hydroxyethyl methacrylate-formylbenzoic acid) [PEG-b-PDMAEMA-b-P(HEMA-FBA)] for the dual delivery of doxorubicin (DOX) and GTI2040 (an antisense oligonucleotide for ribonucleotide reductase inhibition) to MCF-7 breast cancer cells. PEG-b-PDMAEMA-b-PHEMA, the precursor copolymer, was prepared through chain extensions from a PEG-based macroinitiator via two consecutive atom transfer radical polymerization (ATRP) steps. Then, it was modified at the PHEMA block with 4-formylbenzoic acid (FBA) to install reactive aldehyde moieties. A pH-responsive polymer–drug conjugate (PDC) was obtained by conjugating DOX to the polymer structure via acid-labile imine linkages, and subsequently self-assembled in an aqueous solution to form DOX-loaded self-assembled nanoparticles (DOX-SAN) with a positively charged shell. DOX-SAN condensed readily with negatively charged GTI2040 to form GTI2040/DOX-SAN nanocomplexes. Gel-retardation assay confirmed the affinity between GTI2040 and DOX-SAN. The GTI2040/DOX-SAN nanocomplex at N/P ratio of 30 exhibited a volume-average hydrodynamic size of 136.4 nm and a zeta potential of 21.0 mV. The pH-sensitivity of DOX-SAN was confirmed by the DOX release study based on the significant cumulative DOX release at pH 5.5 relative to pH 7.4. Cellular uptake study demonstrated favorable accumulation of GTI2040/DOX-SAN inside MCF-7 cells compared with free GTI2040/DOX. In vitro cytotoxicity study indicated higher therapeutic efficacy of GTI2040/DOX-SAN relative to DOX-SAN alone because of the downregulation of the R2 protein of ribonucleotide reductase. These outcomes suggest that the self-assembled pH-responsive triblock copolymer is a promising platform for combination therapy, which may be more effective in combating cancer than individual therapies.

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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...

Cited by 19 publications

References 64 publications

Cell‐Derived Vesicles for Nanoparticles' Coating: Biomimetic Approaches for Enhanced Blood Circulation and Cancer Therapy

Cell‐Derived Vesicles for Nanoparticles' Coating: Biomimetic Approaches for Enhanced Blood Circulation and Cancer Therapy

Robust Construction of Supersmall Zwitterionic Micelles Based on Hyperbranched Polycarbonates Mediates High Tumor Accumulation

Well-Defined pH-Responsive Self-Assembled Block Copolymers for the Effective Codelivery of Doxorubicin and Antisense Oligonucleotide to Breast Cancer Cells

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