Surfactant tail length dependence of the photophysics and dynamics of a chemotherapeutic drug within anionic micellar aggregates

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

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Self-assembly and sequence length dependence on nanofibrils of polyglutamine peptides

Neuropeptides ◽

10.1016/j.npep.2016.01.011 ◽

2016 ◽

Vol 57 ◽

pp. 71-83 ◽

Cited By ~ 2

Author(s):

Mohammed Inayathullah ◽

Aaron Tan ◽

Rebecca Jeyaraj ◽

James Lam ◽

Nam-Joon Cho ◽

...

Keyword(s):

Self Assembly ◽

Sequence Length ◽

Length Dependence

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Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles

Nature Communications ◽

10.1038/s41467-021-24902-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jing Qi ◽

Feiyang Jin ◽

Yuchan You ◽

Yan Du ◽

Di Liu ◽

...

Keyword(s):

Microwave Irradiation ◽

Antitumor Immunity ◽

Chemotherapeutic Drugs ◽

Chemotherapeutic Drug ◽

A2a Adenosine Receptor ◽

Adenosine Receptor Antagonist ◽

Tumor Immunosuppression ◽

Tumor Immunogenicity ◽

Sch 58261 ◽

Tumor Accumulation

AbstractSome specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge.

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