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This review summarizes engineered “hybrid exosomes” combining exosome biocompatibility with synthetic nanoparticle versatility to enable improved design, higher loading, and targeted tumor delivery, while highlighting recent advances in delivering chemotherapeutics and immunotherapies with enhanced preclinical outcomes and emerging clinical 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problem does the review aim to address in exosome-based cancer therapy?","Question",{"text":63,"@type":64},"It addresses limitations of natural exosomes, especially restricted drug-loading capacity and drug off-targeting, which can lead to ineffective treatment and increased side effects.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How are hybrid exosomes engineered according to the review?",{"text":68,"@type":64},"Hybrid exosomes are engineered by combining the inherent biocompatibility of natural exosomes with the versatility of synthetic nanoparticles to improve delivery and drug loading.",{"name":70,"@type":61,"acceptedAnswer":71},"What therapeutic outcomes does the review report for hybrid exosomes?",{"text":72,"@type":64},"Recent breakthroughs are highlighted showing effective delivery and cellular uptake of chemotherapeutic agents and immunotherapies, with enhanced therapeutic outcomes in preclinical cancer models and emerging clinical 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15th December 2025 DOI: 10.1039/d5ra04927j[rsc.li/rsc-advances](rsc.li/rsc-advances)  \nHybrid exosomes: a rising horizon for precision cancer therapy  \nSwarup Sonar,  a Asmit Das,  a Sidhanti Nyahatkar,b Rajib Dhar,  c Ketki Kalele, d Vinod R. M. T. Balasubramaniam,  a Ling Shing Wong,  e Vinoth Kumarasamy fand Vetriselvan Subramaniyan  *c  \nExtracellular vesicles (EVs) are nanoscale vesicles, which show signiﬁcant promise as biomarkers for cancer diagnosis and prognosis, by providing valuable information about cancer progression and treatment response. Their therapeutic potential (including their popular subset: exosomes) is signiﬁcant, but challenges remain. These limitations with natural exosomes, necessitate innovative engineering strategies. However, current methods for engineering exosomes, such as chimeric and surface modiﬁcations, still need to be improved. A prominent issue is drug oﬀ-targeting, leading to ineﬀective treatment and side eﬀects. To address these challenges, “hybrid exosomes” have been engineered by combining the inherent biocompatibility of natural exosomes with the versatility of synthetic nanoparticles. Cutting-edge design strategies for hybrid exosomes, such as bio-hybrid approaches, emphasize their superior drug loading capacity, and targeted delivery to tumor sites, resulting in minimized toxicity proﬁles. Furthermore, we showcase recent breakthroughs in leveraging hybrid exosomes for the eﬀective delivery and cellular uptake of chemotherapeutic agents and immunotherapies, which oﬀer signiﬁcantly enhanced therapeutic outcomes in preclinical cancer models, with emerging clinical relevance. This review explores the evolving ﬁeld of hybrid exosomes, a novel approach to cancer therapeutics and highlights their potential to overcome existing limitations in cancer treatment. Hybrid exosomes oﬀer a transformative approach to cancer treatment, promising aﬀordable and eﬀective precision therapy with a signiﬁcant impact on cancer therapeutics.  \n1 Introduction  \nThe global shadow cast by cancer continues to lengthen, with the year 2020 alone witnessing a staggering 19.3 million new diagnoses and 10 million lives lost.1 Projections paint an even grimmer picture, forecasting a surge to 28.4 million cases by 2040, driven by a con􀀁uence of population growth and aging.2,3 These stark 􀀃gures underscore the urgent imperative for  \naJeﬀrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia. E-mail: swarup.sonar@ [monash.edu](monash.edu); [asmit.das@monash.edu](asmit.das@monash.edu); [vinod.balasubramaniam@monash.edu](vinod.balasubramaniam@monash.edu)  \n[b](bDepartment of Dentistry)[Department of Dentistry](bDepartment of Dentistry), [VYWS Dental College & Hospital](VYWS Dental College & Hospital), [Amravati](Amravati), [Maharashtra](Maharashtra),  \nIndia. E-mail: [sidhantinyahatkar249@gmail.com](sidhantinyahatkar249@gmail.com)  \ncDivision of Pharmacology, Sir Jeﬀrey Cheah Sunway Medical School, Faculty of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500 Selangor Darul Ehsan, Malaysia. E-mail: [rajib.d@imail.sunway.edu.my](rajib.d@imail.sunway.edu.my); [vetris@sunway.edu](vetris@sunway.edu).  \nmy  \ndDepartment of Oncology, Neuron Institute of Applied Research, Amravati,  \nMaharashtra, India. E-mail: [drketkikalele@gmail.com](drketkikalele@gmail.com)  \neFaculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia. E-mail: [lingshing.wong@newinti.edu.my](lingshing.wong@newinti.edu.my)  \nfDepartment of Parasitology and Medical Entomology, Faculty of Medicine, University Kebangsaan Malaysia, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia. E-mail: [vinoth@ukm.edu.my](vinoth@ukm.edu.my)  \na paradigm shi􀀁 in our approach to cancer diagnosis and treatment.1,3,4 At the heart of cancer's devastating ","cbCaii7KItajrSRK","https://ap.wps.com/l/cbCaii7KItajrSRK","pdf",5861654,18,"English","# Introduction\n## Overview of cancer burden and need for precision therapeutics\n## Role of extracellular vesicles and exosomes\n## Limitations of natural exosomes and rationale for hybrid exosomes\n# Hybrid exosomes: design strategies and therapeutic advantages\n## Bio-hybrid approaches for improved loading and targeting\n## Applications in chemotherapeutic and immunotherapy delivery","[{\"question\":\"What problem does the review aim to address in exosome-based cancer therapy?\",\"answer\":\"It addresses limitations of natural exosomes, especially restricted drug-loading capacity and drug off-targeting, which can lead to ineffective treatment and increased side effects.\"},{\"question\":\"How are hybrid exosomes engineered according to the review?\",\"answer\":\"Hybrid exosomes are engineered by combining the inherent biocompatibility of natural exosomes with the versatility of synthetic nanoparticles to improve delivery and drug loading.\"},{\"question\":\"What therapeutic outcomes does the review report for hybrid exosomes?\",\"answer\":\"Recent breakthroughs are highlighted showing effective delivery and cellular uptake of chemotherapeutic agents and immunotherapies, with enhanced therapeutic outcomes in preclinical cancer models and emerging clinical relevance.\"}]","Hybrid exosomes: a rising horizon for precision cancer therapy | PDF",1790608388,45]