In Vivo Evaluation of Reduction-Responsive Alendronate-Hyaluronan-Curcumin Polymer-Drug Conjugates for Targeted Therapy of Bone Metastatic Breast Cancer

Wang, Kaili; Guo, Caixia; Dong, Xue; Yu, Yueming; Wang, Bingjie; Liu, Wanhui; Chen, Daquan

doi:10.1021/acs.molpharmaceut.8b00266

Cited by 37 publications

(21 citation statements)

References 24 publications

(49 reference statements)

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“…34% reduced size of human breast MDA-MB-231 tumors growing in nude mice injected iv with micelles of hyaluronian-curcumin conjugates as compared to saline-injected animals. However, in this case, mice obtained much higher total doses of curcumin (10 doses of 25 mg curcumin per 1 kg of body mass) than in our studies (4 doses of 3.15 mg curcumin per 1 kg of body mass) 49. Similarly, a conjugate of curcumin with albumin (BSA-Cur) administered intraperitoneally, reduced cancer cells growth by 30% in Dalton’s lymphoma ascites mouse model.…”

Section: Discussioncontrasting

confidence: 61%

<p>Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin</p>

Karabasz¹,

Lachowicz²,

Karewicz³

et al. 2019

IJN

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BackgroundCurcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models.MethodPotential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur.ResultsInjections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas.ConclusionThe tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.

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Section: Discussioncontrasting

confidence: 61%

<p>Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin</p>

Karabasz¹,

Lachowicz²,

Karewicz³

et al. 2019

IJN

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“…The therapeutic efficacy was evaluated by monitoring the tumor volumes in five treated groups every other day and analyzing the histopathological slide after 20 days. And body weights were measured to appraise the drug safety in five treated groups every 2 day [53].…”

Section: Methodsmentioning

confidence: 99%

Protoporphyrin IX-loaded laminarin nanoparticles for anticancer treatment, their cellular behavior, ROS detection, and animal studies

Wang

Guo

et al. 2019

Nanoscale Res Lett

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Laminarin conjugate-based nano-scaled particles were in this study proposed as a delivery system for protoporphyrin IX (Pp IX) in photodynamic therapy (PDT) of human breast cancer cells (MCF-7). Hematin-Laminarin-Dithiodipropionic Acid-MGK, named as HLDM, was an amphiphilic carrier material with dual pH/redox sensitive that could be used to load hydrophobic drug to improve their solubility and enhance biocompatibility. Therefore, we combined photosensitizer (Pp IX) with HLDM to fabricate a novel nano-micelles, herein called Pp IX-loaded HLDM micelles. The Pp IX-loaded HLDM micelles were 149.3 ± 35 nm sized in neutral water. Phototoxicity, in vitro PDT effect, and dual sensibility to pH and redox microenvironment of Pp IX-loaded HLDM micelles were examined at different concentrations by using MCF-7 human breast cancer cells. The experiments on phototoxicity and reactive oxygen species (ROS) production proved that the micelles could produce PDT to kill the cancer cells with a certain wavelength light. The apoptosis experiment indicated that the micelles could cause nuclear damage. In vivo PDT effect of the micelles was studied by constructing the tumor-bearing nude mouse model of MCF-7 cells. In vivo studies showed that the Pp IX-loaded HLDM micelles could induce remarkable anti-tumor effect. A promising laminarin-based nanomedicine platform acts as a new drug delivery system to enhance the uptake, accumulation, and PDT efficacy of Pp IX in vitro and in vivo.

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“…To combat the water-insolubility hurdle of this natural phytomedicine, several approaches were adopted which includes the employment of various carriers, such as polymeric micelles, liposomes, emulsion, nanospheres and polymers ( Allijn et al, 2016 , Zhao et al, 2017 , Zhu et al, 2017 ). In particular, conjugation of curcumin with hyaluronic acid has received appreciable attention in recent times not only for increasing bioavailability but also to target tumor cells and tumor metastases for the treatment of numerous cancer ( Saravanakumar et al, 2014 , Wang et al, 2018 ).…”

Section: Motivationmentioning

confidence: 99%

Degree-based topological indices and polynomials of hyaluronic acid-curcumin conjugates

Ali

Kirmani

Rugaie

et al. 2020

Saudi Pharmaceutical Journal

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Quantitative structure–activity relationship (QSAR) represents quantitative correlation of chemical structural features called as molecular descriptors and pharmacological activity as response endpoints. Topological index is a molecular descriptor extensively used to study QSAR of pharmaceuticals to assess their molecular characteristics by numerical computation. Theoretical assessment of drug like molecules helps to expedite the drug design and discovery process by rationalizing the lead identification, lead optimization and understanding their mechanism of actions. Therefore, in this article, we have computed the general inverse sum indeg index, of Hyaluronic acid-curcumin conjugates by using molecular structure analysis and edge partitioning technique. Many standard topological indices are obtained as a special case of . We also proposed general inverse sum indeg polynomial of Hyaluronic acid-curcumin conjugates from which many well-known polynomials are deduced.

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In Vivo Evaluation of Reduction-Responsive Alendronate-Hyaluronan-Curcumin Polymer-Drug Conjugates for Targeted Therapy of Bone Metastatic Breast Cancer

Cited by 37 publications

References 24 publications

<p>Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin</p>

<p>Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin</p>

Protoporphyrin IX-loaded laminarin nanoparticles for anticancer treatment, their cellular behavior, ROS detection, and animal studies

Degree-based topological indices and polynomials of hyaluronic acid-curcumin conjugates

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