Impact of Poly(Ester Amide) Structure on Properties and Drug Delivery for Prostate Cancer Therapy

Objective:We aim to develop a polymer library consisting of phenylalanine-based poly(ester amide)s(Phe-PEAs)for cancer therapy and investigate the structure–property relationship of these polymers to understand their impact on the drug delivery efficiency of corresponding nanoparticles(NPs).Impact Statement:Our study provides insights into the structure–property relationship of polymers in NP-based drug delivery applications and offers a potential polymer library and NP platform for enhancing cancer therapy.Introduction:Polymer NP-based drug delivery systems have demonstrated substantial potential in cancer therapy by improving drug efficacy and minimizing systemic toxicity.However,successful design and optimization of these systems require a comprehensive understanding of the relationship between polymer structure and physicochemical properties,which directly influence the drug delivery efficiency of the corresponding NPs.Methods:A series of Phe-PEAs with tunable structures was synthesized by varying the length of the methylene group in the diol part of the polymers.Subsequently,Phe-PEAs were formulated into NPs for doxorubicin(DOX)delivery in prostate cancer therapy.Results:Small adjustments in polymer structure induced the changes in the hydrophobicity and thermal properties of the PEAs,consequently NP size,drug loading capacity,cellular uptake efficacy,and cytotoxicity.Additionally,DOXloaded Phe-PEA NPs demonstrated enhanced tumor suppression and reduced side effects in prostate tumor-bearing mice.Conclusion:Phe-PEAs,with their finely tunable structures,show great promise as effective and customizable nanocarriers for cancer therapy.

Inflammatory Factor IL1αInduces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca^(2+)/CaMK2b Pathway

Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI is unclear.Grin2c(glutamate ionotropic receptor type 2c)plays an essential role in cell proliferation.Our bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after SCI.Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in vitro.By screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage model.Blockade of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI.Overall,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.

Dysregulation and implications of N6-methyladenosine modification in renal cell carcinoma

Increasing evidence indicates that N6-methyladenosine(m6A)methylation modification serves important functions in biological metabolism.Dysregulation of m6A regulators is related to the progression of different malignancies,including renal cell carcinoma(RCC).Recent studies have reported preliminary findings on the influence of m6A regulator dysregulation on RCC tumorigenesis and development.However,no comprehensive review that integrates and analyzes the roles of m6A modification in RCC has been published to date.In this review,we focus on the dysregulation of m6A regulators as it relates to RCC tumorigenesis and development,as well as possible applications of m6A modification in RCC diagnosis and therapeutics.