The enhanced antitumor activity of the polymeric conjugate covalently coupled with docetaxel and docosahexaenoic acid

Dong, Peiwu; Liu, Jiaojiao; Lv, Hongshuai; Wu, Jiaan; Zhang, Naining; Wang, Si; Li, Xiaohai; Hu, Jinghua; Wang, Anny; Li, Daisy J; Wang, Dandan; Cao, Shengnan; Xie, Liangyu; Shi, Yikang

doi:10.1039/d2bm00337f

Cited by 6 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the end of the experiment, 6 mg/kg parent DTX treatment inhibited tumor growth by 16.2%, while the conjugate 18 treatment at the dose of 6 and 12 mg/kg inhibited tumor growth by 32.6% and 59.0%, respectively ( Figure 6(A,C) ). The tumor growth inhibitory efficacy of the conjugate 18 was similar to that of tandem type of dual-drug conjugate we reported previously (Dong et al., 2022 ). Our previous study showed that the treatment of 6 mg/kg of parent DTX, 6 mg/kg and 12 mg/kg of tandem type of dual-drug conjugate decreased the tumor volume by 19.6%, 36.8%, and 58.8% in H460 xenograft under the same schedule of administration as this study, respectively.…”

Section: Resultssupporting

confidence: 84%

“…Surprisingly, 12 mg/kg of conjugate 18 eradicated all the tumors on day 18 ( Figure 6(F) ). The antitumor effect of the conjugate 18 exceeded that of tandem type of dual-drug conjugate we reported previously, in which the treatment of tandem type of dual-drug conjugate with the dose of 12 mg/kg eliminated 4 out 6 xenograft tumors in MCF-7 bearing nude mice after four times of administration once a week (Dong et al., 2022 ). The single-drug conjugate dextran-DTX at the dose of 12 mg/kg eradicated 2 tumors on day 18 and 5 tumors on day 21 ( Figure 6(F) ).…”

Section: Resultsmentioning

confidence: 68%

“…We have previously produced a dual-drug conjugate dextran–DHA–DTX by first connecting DHA and DTX to form DHA–DTX, and then grafting DHA–DTX onto dextran (Dong et al., 2022 ). However, in this study, a dual-drug conjugate dextran–DHA–DTX was produced by separately connecting DHA and DTX with dextran through individual linkers, which was completely different in chemical structure from tandem type of dual-drug conjugate we reported previously.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Polysaccharide dextran-based conjugate for selective co-delivery of two synergistic drugs docetaxel and docosahexaenoic acid to tumor cells

Dong

Wang

et al. 2022

Drug Delivery

Self Cite

View full text Add to dashboard Cite

Most chemotherapeutic agents are nonspecific distribution and cause systemic toxicities. Polysaccharide-based conjugates are promising strategies to overcome these drawbacks. To this end, two synergistic drugs docetaxel (DTX) and docosahexaenoic acid (DHA) were independently covalently bonded through individual linkers to dextran (100 kDa) to produce a novel dual-drug conjugate dextran–DHA–DTX. The single-drug conjugates dextran–DHA and dextran–DTX were also prepared for comparison. Fluorescent dye Cy7.5-based conjugates dextran–Cy7.5 and dextran–DHA–Cy7.5 were synthesized for cellular uptake study. The dual-drug conjugate dextran–DHA–DTX self-assembled into nanoparticles with the diameter of 102.3 ± 8.3 nm and demonstrated enhanced water solubility and improved pharmacokinetic profiles. Cellular uptake results showed that the dual-drug conjugate entered cells more than the parent DTX by determining the intracellular DTX contents via HPLC/MS analysis and by determining the fluorescent intensity of dextran-Cy7.5 and dextran–DHA–Cy7.5. Importantly, the dual-drug conjugate dextran–DHA–DTX significantly accumulated in tumor tissues and dramatically reduced the DTX concentrations in normal tissues. The dual-drug conjugate completely eradicated all the MCF-7 xenograft tumors without obvious side effects and showed more superior antitumor activity than parent DTX and single-drug conjugate dextran–DTX and dextran–DHA. Both in vitro and in vivo studies showed that DHA enhanced the antitumor activity of dextran–DTX. The polysaccharide dextran-based dual-drug conjugates may represent an effective way to improve the chemotherapeutic agents.

show abstract

Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polysaccharide dextran-based conjugate for selective co-delivery of two synergistic drugs docetaxel and docosahexaenoic acid to tumor cells

Dong

Wang

et al. 2022

Drug Delivery

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, it can hinder tumor invasion and metastasis by reducing tumor cell rolling, adhesion, and migration. Importantly, previous research has shown that DHA can increase the susceptibility of cancer cells to chemotherapeutic agents without amplifying the toxicity to healthy tissues [ 209 , 210 ]. Both of these factors have prompted researchers to incorporate marine-derived PUFAs into drug delivery systems as assemblers or drug loaders for the purpose of synthetically enhancing cancer treatment.…”

Section: Marine Food Sources-derived Fatty Acid-based Nanomaterialsmentioning

confidence: 99%

Marine biomaterials in biomedical nano/micro-systems

Wang,

Chen,

Wang

et al. 2023

J Nanobiotechnol

View full text Add to dashboard Cite

Marine resources in unique marine environments provide abundant, cost-effective natural biomaterials with distinct structures, compositions, and biological activities compared to terrestrial species. These marine-derived raw materials, including polysaccharides, natural protein components, fatty acids, and marine minerals, etc., have shown great potential in preparing, stabilizing, or modifying multifunctional nano-/micro-systems and are widely applied in drug delivery, theragnostic, tissue engineering, etc. This review provides a comprehensive summary of the most current marine biomaterial-based nano-/micro-systems developed over the past three years, primarily focusing on therapeutic delivery studies and highlighting their potential to cure a variety of diseases. Specifically, we first provided a detailed introduction to the physicochemical characteristics and biological activities of natural marine biocomponents in their raw state. Furthermore, the assembly processes, potential functionalities of each building block, and a thorough evaluation of the pharmacokinetics and pharmacodynamics of advanced marine biomaterial-based systems and their effects on molecular pathophysiological processes were fully elucidated. Finally, a list of unresolved issues and pivotal challenges of marine-derived biomaterials applications, such as standardized distinction of raw materials, long-term biosafety in vivo, the feasibility of scale-up, etc., was presented. This review is expected to serve as a roadmap for fundamental research and facilitate the rational design of marine biomaterials for diverse emerging applications. Graphical Abstract

show abstract

“…One of the explored strategies is that of combining the treatment with DTX with that of other antineoplastic agents [21,22]. One possible combination strategy that has been largely explored in breast cancer and has been shown to induce a considerable increase in the DTX antineoplastic efficacy is the combined treatment of DTX with omega-3 polyunsaturated fatty acids (PUFAs) and, in particular, with the long-chain omega-3 PUFA docosahexaenoic acid (DHA, 22:6 n-3) [23][24][25] which is a natural compound present in our diet. It is incorporated at high levels in our cellular membranes and is devoid of side effects [26].…”

Section: Introductionmentioning

confidence: 99%

ROS-Responsive PLGA-NPs for Co-Delivery of DTX and DHA for Colon Cancer Treatment

Cassano,

Trombino,

Curcio

et al. 2024

IJTM

View full text Add to dashboard Cite

The aim of this work was to evaluate the antineoplastic effect of newly synthesized nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) alone or PLGA esterified with 2,2′-[propane-2,2-diylbis (thio)] diacetic acid (TKL), loaded with docetaxel (DTX) and/or docosahexaenoic acid (DHA), as innovative site-specific therapeutic carriers. The obtained materials were characterized by FT-IR and 1H-NMR, while the dimensional analysis of the nanoparticles obtained was performed by Dynamic Light Scattering. The encapsulation efficiency of the nanoparticles was evaluated, and in vitro skin permeation tests were also performed. The antitumor activity of the nanomaterial was studied in the human adenocarcinoma HCT116 cell line. In particular, viability tests in bidimensional culture, as well as in tumor spheroids, were conducted. The use of these nanocarriers could facilitate the stable and efficient delivery of DTX and DHA through the upper segments of the gastrointestinal tract to the colon. In addition, the presence of the ROS-sensitive 2,2′-[propane-2,2-diylbis (thio)] diacetic acid in their matrix should promote the site-specific release of DTX in the tumor mass, where high levels of reactive oxygen species could be found.

show abstract

The enhanced antitumor activity of the polymeric conjugate covalently coupled with docetaxel and docosahexaenoic acid

Abstract: Docetaxel (DTX) has been widely used for treatment of many types of cancer. However, DTX is poor water soluble and commercial DTX is formulated in nonionic surfactant polysorbate 80 and...

Cited by 6 publications

References 44 publications

Polysaccharide dextran-based conjugate for selective co-delivery of two synergistic drugs docetaxel and docosahexaenoic acid to tumor cells

Polysaccharide dextran-based conjugate for selective co-delivery of two synergistic drugs docetaxel and docosahexaenoic acid to tumor cells

Marine biomaterials in biomedical nano/micro-systems

ROS-Responsive PLGA-NPs for Co-Delivery of DTX and DHA for Colon Cancer Treatment

Contact Info

Product

Resources

About