THERAPEUTIC DELIVERY IN GENOMIC CANCER CARE

It involves utilizing genetic information to design and administer treatment tailored to an individual's specific genetic makeup. This personalized approach aims to enhance treatment efficacy while minimizing adverse effects [126, 127]. Targeted therapy in cancer treatment involves using drugs or substances that specifically interfere with molecules crucial for cancer cell growth and spread. It focuses on identifying the unique characteristics of cancer cells and minimizing harm to healthy cells. Before treatment, molecular profiling of the tumor is conducted to pinpoint specific targets for therapy, such as proteins, receptors, or genetic mutations [10, 128]. Various types of targeted therapies, including small-molecule drugs and monoclonal antibodies, aim to disrupt these identified targets, such as Herceptin for HER2-positive breast cancer or imatinib for certain genetic mutations in leukemia [129].

Guo _et al. (_2019) developed a technique using antibodies and nanolipogels to deliver CRISPR-associated protein 9 (CRISPR/Cas9) plasmids directly into triple-negative breast cancer cells. By targeting the Lipocalin 2 gene, they achieved approximately 81% suppression efficiency, resulting in a 77% reduction in the growth rate of the tumor. This suggests that the tumor-targeted nanolipogel system acts as an efficient and precise delivery strategy for CRISPR-based genome editing customized for specific targets [130]. The delivery of modified genes to cancer cells comprises numerous methods that aim for precise and targeted transference of altered genetic material to target cells, such as viral vectors, non-viral vectors, electroporation, gene gun technology, CRISPR/Cas9 delivery systems, and injectable hydrogels. Viral vectors are used to transport therapeutic genes into cancer cells, such as adenoviruses, lentiviruses, and adeno-associated viruses, while non-viral vectors consist of synthetic carriers like liposomes, polymers, or nanoparticles that encapsulate and transport genetic payloads. Electroporation uses an electric field to produce temporary pores in the cell membrane, facilitating gene entry, whereas the gene gun method propels modified genetic material-coated particles into cells. The CRISPR/Cas9 system can be delivered via viral or non-viral vectors for precise genome editing within cancer cells. Injectable hydrogels consist of genetic materials that are directly administered for the controlled release of therapeutic genes specifically targeting cancer cells within the tumor microenvironment. These varied methodologies exhibit distinct advantages and limitations in terms of efficiency, specificity, safety, and scalability, warranting ongoing research and refinement for improved efficacy and reduced off-target effects in gene delivery to cancer cells. Drug delivery systems are pivotal in genomic cancer care, revolutionizing treatment precision by transporting therapeutic agents to specific cells or tissues based on genetic markers [130]. Nanoparticles, minute particles engineered typically within the range of 1 to 100 nm, offer targeted drug delivery by binding to receptors or proteins overexpressed in tumor cells, minimizing side effects while maximizing drug efficacy [131-134]. Liposomes, lipid-based vesicles, possess versatility in encapsulating diverse drugs and can be tailored to target specific cancer cells, ensuring biocompatibility and customizable sizes for optimal circulation and uptake [135]. Polymer-based systems, utilizing biodegradable polymers, allow for controlled drug release and targeted delivery, enabling customization for sustained therapeutic impact [136]. These systems hold promise in refining cancer treatments, yet their development necessitates stringent testing and personalized approaches to match individual genetic profiles and cancer characteristics for clinical application.

Liu et al. (2018) developed a dual-targeted delivery system using polymer and inorganic hybrid nanoparticles. It comprised a CRISPR/Cas9 plasmid targeting Cyclin-Dependent Kinase 11 (CDK11), which was encapsulated within the core of nanoparticles composed of protamine sulfate, calcium carbonate, calcium phosphate, and carboxymethyl chitosan. The S1411 aptamer ligands synergistically interact through electrostatic interactions to enhance binding [137]. Furthermore, combinatorial approaches in cancer therapy involve treatments based on a patient’s genetic profile to maximize effectiveness and minimize resistance within cancer cells, such as targeted therapy, immunotherapy, chemotherapy, or radiation [138]. By targeting multiple pathways simultaneously and potentially generating synergistic effects, these combinations aim to overcome resistance mechanisms and reduce the likelihood of cancer cells adapting to treatment [139]. Moreover, by using lower doses of individual drugs and selectively targeting tumor vulnerabilities, these approaches seek to minimize side effects on healthy tissues [140]. Continuous monitoring and dynamic adjustments to treatment plans based on tumor responses further optimize efficacy. However, challenges such as the complexity of treatment design, cost, and accessibility persist, necessitating ongoing research and clinical validation to fully harness the potential of these personalized combinations in cancer care [10]. The current genomic approaches are listed in Table 5.