Cryptosomes are a promising medication delivery mechanism that improves stability, bioavailability, and targeted administration of pharmaceuticals. These lipid-based nanocarriers can encapsulate hydrophilic and hydrophobic medicines, making them useful for various therapeutic purposes. This review covers cryptosome features, preparation, and drug delivery applications, discussing lipid composition, surface modification, and encapsulation efficiency. Recent improvements have shown promise in improving medicinal efficacy and patient compliance. To accelerate bench-to-bedside translation, scale-up production, and regulatory issues are addressed. Cryptosomes are a promising drug delivery research frontier, with future research aiming to enhance treatment outcomes and eliminate side effects.

Tumor Microenvironment (TME) is a major determinant of tumor progression, immune evasion, metastasis, and therapeutic resistance, yet its complexity remains inadequately represented by conventional preclinical models. Two-dimensional cell cultures and animal models often fail to reproduce the cellular heterogeneity, biomechanical forces, vascular architecture, and dynamic biochemical gradients of human tumors, limiting their predictive value for clinical translation. Patients derived organoids (PDOs) and organ-on-chip (OoC) technology has recently been developed to create biomimetic platforms retaining patient-specific tumor characteristics and reproducing physiologically relevant tumor microenvironments by the control of tumor microenvironment perfusion. The review highlights the potential of using the organoid-on-chip approach to combine with nanomedicine for the next generation of precision oncology approaches to engineering the TME. We emphasize the engineering principles of organoid-on-chip platforms such as shear stress, oxygen and nutrient gradients, extracellular matrix remodeling, and multicellular interactions, which are all important factors in regulating the behavior of tumors. Special focus is on the mechanism of transport of nanoparticles, cellular uptake, intracellular trafficking, endosomal escape, and drug release in TME, which are relevant to acidic pH, hypoxia, ROS, enzymes, glutathione and ATP. The review also explores the current strategies for TME engineering which include extracellular matrix remodeling, immune reprogramming, vascular normalization, metabolic modulation, and biomechanical regulation. Additionally, recent innovations combining AI, digital twin, multi-omics, spatial transcriptomics, single-cell sequencing, and high-content imaging with organoid-on-a-chip platforms are presented as promising solutions for designing nanoparticles for better therapeutic efficacy, predicting responses to drugs, and personalized drug screening. Organoid-on-chip-guided nanomedicine holds great promise as a clinically relevant and effective platform for predictive cancer modeling, for rapid drug development, and for personalized precision oncology. Graphical Abstract

Cancer is not only a modern disease but an evolutionary condition shaped by long-term genetic and epigenetic changes. Research in archaeogenetics and ancient DNA (aDNA) provides new insights into how inherited mutations, viral elements, and environmental exposures have influenced cancer risk over thousands of years. This review explores how ancient genomic and epigenomic evidence contributes to understanding the origins of cancer and its relevance to modern clinical oncology. Evidence from skeletal and mummified remains confirms that malignancies existed long before industrialization. Ancient genomes reveal hereditary risk variants in cancer-related genes such as BRCA and TP53, suggesting that genetic susceptibility to cancer has deep evolutionary roots. Importantly, reconstructed DNA methylation patterns from ancient samples indicate that epigenetic regulation of tumor suppressor genes and oncogenic pathways has been conserved across time. Human endogenous retroviruses (HERVs), integrated into the human genome during evolution, show epigenetic activation in several cancers and may serve as potential biomarkers or therapeutic targets. Comparative analyses further demonstrate both stable mutational processes and environmentally influenced epigenetic shifts. Overall, integrating ancient epigenomic data with modern multi-omics approaches enhances our understanding of cancer biology. This evolutionary and epigenetic perspective may support biomarker discovery, improve risk stratification, and guide the development of targeted and immunotherapeutic strategies in precision oncology.