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Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

Oncology Research 2024年第5期32卷 877-897页

作者： KARAN WADHWA PAYAL CHAUHAN SHOBHIT KUMAR RAKESH PAHWA RAVINDER VERMA RAJAT GOYAL GOVIND SINGH ARCHANA SHARMA NEHA RAO DEEPAK KAUSHIK department of pharmaceutical sciences Maharshi Dayanand UniversityRohtak124001India department of pharmaceutical technology Meerut Institute of Engineering and Technology(MIET)NH-58Delhi-Roorkee HighwayMeerut250005India Institute of pharmaceutical sciences Kurukshetra UniversityKurukshetra136119India department of pharmaceutical sciences Chaudhary Bansi Lal UniversityBhiwani127021India MM College of Pharmacy Maharishi Markandeshwar(Deemed to be University)Mullana-AmbalaHaryana133207India Delhi pharmaceutical sciences and Research University(DIPSAR) Delhi Pharmaceutical Sciences and Research UniversityNew Delhi110017India

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive tumor.The high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the tumormass.Objective:Recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation therapy.Methods:Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several others.Conclusion:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management.Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

关键词： Glioblastoma Brain tumor Blood-brain barrier Liposomes Metallic nanoparticles Nanocarriers

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A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent Prunus species of southeast Asia

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Journal of Traditional Chinese Medicine 2024年第3期44卷 620-628页

作者： Shikha Agrawal Adarsh Kumar Ankit Kumar Singh Harshwardhan Singh Suresh Thareja Pradeep Kumar department of pharmaceutical sciences and Natural Products Central University of Punjab

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian subcontinent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent,it extends from the Himalayas to Sikkim, Meghalaya,Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological,microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory,hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus species from its distribution, morphological characters to phytoconstituents, and pharmacological activity.

关键词： Prunus Rosaceae antineoplastic agents distribution hypoglycemic agents phytochemistry review

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Immune checkpoint inhibitors:breakthroughs in cancer treatment

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Cancer Biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of Immunology and Inflammation School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University department of Biology School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade(ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies(mAbs) are currently available as immune checkpoint inhibitors(ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4) and programmed cell death protein 1(PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response.Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1(anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains(TIGIT), mucin domain containing-3(TIM-3), lymphocyte activation gene-3(LAG-3), V-domain immunoglobulin suppressor of T cell activation(VISTA), B and T lymphocyte attenuator(BTLA), and signal-regulatory protein α(SIRPα). Functional m Abs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： CTLA-4 ICIs Immunotherapy PD-1 cancer

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Bile acid metabolism and signaling in health and disease:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2014-2064页

作者： Joshua S.Fleishman Sunil Kumar department of pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA

Bile acids,once considered mere dietary surfactants,now emerge as critical modulators of macronutrient(lipid,carbohydrate,protein)metabolism and the systemic pro-inflammatory/anti-inflammatory balance.Bile acid metabolism and signaling pathways play a crucial role in protecting against,or if aberrant,inducing cardiometabolic,inflammatory,and neoplastic conditions,strongly influencing health and disease.No curative treatment exists for any bile acid influenced disease,while the most promising and well-developed bile acid therapeutic was recently rejected by the FDA.Here,we provide a bottom-up approach on bile acids,mechanistically explaining their biochemistry,physiology,and pharmacology at canonical and non-canonical receptors.Using this mechanistic model of bile acids,we explain how abnormal bile acid physiology drives disease pathogenesis,emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic diseases.We provide an in-depth summary on pre-existing bile acid receptor modulators,explain their shortcomings,and propose solutions for how they may be remedied.Lastly,we rationalize novel targets for further translational drug discovery and provide future perspectives.Rather than dismissing bile acid therapeutics due to recent setbacks,we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.

关键词： metabolism rejected shortcomings

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Critical Review on Balanites aegyptiaca Delile: Phytoconstituents, Pharmacological Properties and Nanointerventions

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Chinese Journal of Integrative Medicine 2024年第7期30卷 653-663页

作者： Surendra Kumar Gautam Rakesh Kumar Paul Devesh M.Sawant Amita Sarwal Kaisar Raza department of Pharmacy School of Chemical Sciences and Pharmacy Central University of Rajasthan University Institute of pharmaceutical sciences Panjab University

Balanites aegyptiaca Delile(BA) is an enduring xerophytic woody and spinous flowering tree and is commonly known as desert date or Ingudi(Hingot). It belongs to the family Zygophyllaceae, which is specific to be drought areas of Nigeria, Africa, South Asia and India(Rajasthan). In Ayurveda, this traditional medicinal plant is reported for the management of jaundice, syphilis, yellow fever, metabolic disorders, liver, and spleen problems. The main aim of the review is to compile its medicinal uses and further advancements to showcase the promises inherited in various parts of the plant for the benefit of mankind. As per the literature survey, various researchers have focused on the detailed investigation of BA including the phytopharmacological evidence, chemical constituents, nano-formulations, commercialized products, and clinical trials. Several remarkable scaffolds and isolated compounds like diosgenin, yamogenin, balanitin1/2, balanitin 3, bal4/5, bal6/7, rutin-3-glycosides, 3,7-diglycosides,(3, 12, 14, 16)–(12-hydroxycholest-5-ene-3,16-diyl-bis)-D-glucopyranoside and balanitoside have been identified. Additionally, this traditional plant has been scientifically proven by in vitro and in vivo. Based on the complete review of this plant, most of the compounds have been isolated from the fruit and kernel part. Additionally, based on the literature, a histogram was developed for pharmacological activity in which antidiabetic study was found to be more compared to other pharmacological activity. As a spinous desert dates, this plant needs to be explored more to bring out newer phytochemicals in the management of various diseases.

关键词： Delile desert date phytochemicals nano-phytopharmaceutical pharmacological activities traditional medicine

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Pharmacological potential of Manilkara zapota(L.)P.Royen(Sapodilla):a narrative review

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Journal of Traditional Chinese Medicine 2024年第2期44卷 403-407页

作者： Priyanka Sharma Aakash Deep Harish Kumar Nitin Bansal Sanjiv Kumar Arun Davinder Kumar department of pharmaceutical sciences Chaudhary Bansi Lal UniversityBhiwani 127021India department of pharmaceutical sciences Maharishi Dayanand UniversityRohtak 124001India

Herbal medicine is safe and effective in treating various diseases.Traditional herbal medicine plays a tremendous role in treatment of various diseases and accompanying complications,hence herbal medicine requires remarkable attention in further research for the development of numerous active formulations for treatment of health troubles.The plant needs special consideration for development and research of unidentified compound and characterization of novel active molecules that overcome multiple pathological abnormalities.The genus Manilkara contains 135 plants around the world.This overview discusses all the virtues of most important and commonly used plant Manilkara zapota(L.)P.Royen(M.zapota),also known as Sapodilla.M.zapota has various traditional beneficial effects in treatment of various diseases and disorders dating back to prehistoric times and used in ancient traditional system of herbal medicine.

关键词： herbal medicine Manilkara zapota phytoconstituents pharmacological activity review

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Recent updates on nano-phyto-formulations based therapeutic intervention for cancer treatment

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Oncology Research 2024年第1期32卷 19-47页

作者： ABHISHEK WAHI MAMTA BISHNOI NEHA RAINA MEGHNA AMRITA SINGH PIYUSH VERMA PIYUSH KUMAR GUPTA GINPREET KAUR HARDEEP SINGH TULI MADHU GUPTA department of Pharmaceutics School of Pharmaceutical SciencesDelhi Pharmaceutical Sciences and Research University(DPSRU)Pushp ViharNew Delhi110017India department of pharmaceutical sciences Gurugram UniversityHaryana122003India department of Life sciences Sharda School of Basic Sciences and ResearchSharda UniversityGreater NoidaUttar Pradesh201310India department of Biotechnology Graphic Era(Deemed to be University)DehradunUttarakhand248002India department of Pharmacology Shobhaben Pratapbhai Patel School of Pharmacy&Technology ManagementSVKM’s NMIMSVile Parle(West)Mumbai400056India department of Bio-sciences and technology Maharishi Markandeshwar Engineering CollegeMaharishi Markandeshwar(Deemed to be University)MullanaAmbala133207India

Cancer is a leading cause of death globally,with limited treatment options and several limitations.Chemotherapeutic agents often result in toxicity which long-term conventional treatment.Phytochemicals are natural constituents that are more effective in treating various diseases with less toxicity than the chemotherapeutic agents providing alternative therapeutic approaches to minimize the resistance.These phytoconstituents act in several ways and deliver optimum effectiveness against cancer.Nevertheless,the effectiveness of phyto-formulations in the management of cancers may be constrained due to challenges related to inadequate solubility,bioavailability,and stability.Nanotechnology presents a promising avenue for transforming current cancer treatment methods through the incorporation of phytochemicals into nanosystems,which possess a range of advantageous characteristics such as biocompatibility,targeted and sustained release capabilities,and enhanced protective effects.This holds significant potential for future advancements in cancer management.Herein,this review aims to provide intensive literature on diverse nanocarriers,highlighting their applications as cargos for phytocompounds in cancer.Moreover,it offers an overview of the current advancements in the respective field,emphasizing the characteristics that contribute to favourable outcomes in both in vitro and in vivo settings.Lastly,clinical development and regulatory concerns are also discussed to check on the transformation of the concept as a promising strategy for combination therapy of phytochemicals and chemotherapeutics that could lead to cancer management in the future.

关键词： Phyto-formulations Cancer Nanocarriers Nanotechnology Clinical development

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Probing the endoplasmic reticulummitochondria interaction in Alzheimer's disease:searching far and wide

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Neural Regeneration Research 2024年第10期19卷 2103-2104页

作者： Giulia Dematteis Laura Tapella Dmitry Lim department of pharmaceutical sciences Universitàdel Piemonte Orientale“Amedeo Avogadro”NovaraItaly

Alzheimer's disease(AD)is the most frequent,form of dementia in elderly people and is an incurable disease with an exponentially growing number of cases.Extracellular deposition of amyloid-β(Aβ)plaques and intraneur... 详细信息

关键词： Alzheimer Aβ reticulum

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Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

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Asian Journal of pharmaceutical sciences 2024年第2期19卷 170-187页

作者： Bao Li Haoran Niu Xiaoyun Zhao Xiaoyu Huang Yu Ding Ke Dang Tianzhi Yang Yongfeng Chen Jizhuang Ma Xiaohong Liu Keda Zhang Huichao Xie Pingtian Ding School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang pharmaceutical University Shenyang 110016 China department of Basic pharmaceutical sciences School of Pharmacy Husson University Bangor ME 04401USA College of Pharmacy Shenzhen Technology UniversityShenzhen 518118China

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

关键词： Anti-angiogenesis Tumor apoptosis Nanoparticles VEGF siRNA Hypoxia inducible factor(HIF)-1 protein Phenethyl isothi ocyanate(PEITC)

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Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India department of Pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia department of Pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China department of pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

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