# Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy **Authors:** Rouba D. Al Bostami, Waad H. Abuwatfa, Ghaleb A. Husseini PMC · DOI: 10.3390/nano12152672 · 2022-08-04 ## TL;DR This review discusses how combining multiple cancer treatments using nanoparticles can improve therapy effectiveness and reduce side effects. ## Contribution The paper provides a comprehensive overview of recent advances in nanoparticle-based co-delivery systems for cancer therapy. ## Key findings - Nanoparticle-based co-delivery systems enhance the synergistic effects of multiple drugs and genes. - Multidrug-loaded nanocarriers offer potential for improved cancer suppression with fewer side effects. - Designing co-delivery systems requires understanding drug ratios and cancer cell heterogeneity. ## Abstract Cancer therapies have advanced tremendously throughout the last decade, yet multiple factors still hinder the success of the different cancer therapeutics. The traditional therapeutic approach has been proven insufficient and lacking in the suppression of tumor growth. The simultaneous delivery of multiple small-molecule chemotherapeutic drugs and genes improves the effectiveness of each treatment, thus optimizing efficacy and improving synergistic effects. Nanomedicines integrating inorganic, lipid, and polymeric-based nanoparticles have been designed to regulate the spatiotemporal release of the encapsulated drugs. Multidrug-loaded nanocarriers are a potential strategy to fight cancer and the incorporation of co-delivery systems as a feasible treatment method has projected synergistic benefits and limited undesirable effects. Moreover, the development of co-delivery systems for maximum therapeutic impact necessitates better knowledge of the appropriate therapeutic agent ratio as well as the inherent heterogeneity of the cancer cells. Co-delivery systems can simplify clinical processes and increase patient quality of life, even though such systems are more difficult to prepare than single drug delivery systems. This review highlights the progress attained in the development and design of nano carrier-based co-delivery systems and discusses the limitations, challenges, and future perspectives in the design and fabrication of co-delivery systems. ## Linked entities - **Diseases:** cancer (MONDO:0004992) ## Full-text entities - **Genes:** SEMA6D (semaphorin 6D) [NCBI Gene 80031], MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Trf (transferrin) [NCBI Gene 22041] {aka Cd176, HP, Tf, Tfn, hpx}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], ITGA7 (integrin subunit alpha 7) [NCBI Gene 3679], ABCG2 (ATP binding cassette subfamily G member 2 (JR blood group)) [NCBI Gene 9429] {aka ABC15, ABCP, BCRP, BMDP, CD338, CDw338}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, ASCL1 (achaete-scute family bHLH transcription factor 1) [NCBI Gene 429] {aka ASH1, HASH1, MASH1, bHLHa46}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, TFRC (transferrin receptor) [NCBI Gene 7037] {aka CD71, IMD46, T9, TFR, TFR1, TR}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, glutathione synthetase [NCBI Gene 101084439], NR1H3 (nuclear receptor subfamily 1 group H member 3) [NCBI Gene 10062] {aka LXR-a, LXRA, RLD-1} - **Diseases:** SCC (MESH:D018307), nasopharyngeal cancer (MESH:D009303), immunodeficient (MESH:D007153), Head and neck cancer (MESH:D006258), melanoma (MESH:D008545), neuroendocrine tumors (MESH:D018358), Non-Hodgkin Lymphoma (MESH:D008228), Brain cancer (MESH:D001932), Lung cancerRecurrent (MESH:D008171), Ovarian cancer (MESH:D010051), Colorectal cancer (MESH:D015179), MDR (MESH:D018088), thrombosis (MESH:D013927), Liver (MESH:D017093), Lymphomatous meningitis (MESH:D013967), cardiotoxicity (MESH:D066126), Glioblastoma multiforme (MESH:D005909), pancreatic adenocarcinoma (MESH:D010190), adenocarcinoma of the pancreas (MESH:D000230), Non-small lung cancer (MESH:D002289), hematologic malignancies (MESH:D019337), -cancer (MESH:D009369), Osteosarcoma (MESH:D012516), endothelial injury (MESH:D057772), mitochondrial damage (MESH:D028361), Kaposi's sarcoma (MESH:D012514), Glioblastoma, prostate, and pancreatic cancer (MESH:D011471), Lung cancer (MESH:D008175), Renal cancer (MESH:D007680), multiple myeloma (MESH:D009101), -drug resistance (MESH:D000069279), Gastric, prostate, and ovarian cancer (MESH:D011472), Cervical carcinoma (MESH:D002583), Ovarian, breast, and lung cancers (MESH:D061325), epidermoid carcinoma (MESH:D002294), nasopharyngeal carcinoma (MESH:D000077274), Oral squamous carcinoma (MESH:D000077195), Breast cancer (MESH:D001943), EPR (MESH:C564835), cardiovascular diseases (MESH:D002318), cytotoxicity (MESH:D064420), Hepatocellular carcinoma (MESH:D006528), Acute lymphocytic leukemia (MESH:D054198), death (MESH:D003643), acute myeloid leukemia (MESH:D015470) - **Chemicals:** floxuridine (MESH:D005467), gemcitabine (MESH:D000093542), hyaluronic acid (MESH:D006820), carbonate apatite (MESH:C030782), daunorubicin (MESH:D003630), Lipid (MESH:D008055), free radicals (MESH:D005609), silicon (MESH:D012825), Temozolomide (MESH:D000077204), Au (MESH:D006046), mPEG-PLGA (MESH:C558447), PEI (MESH:C505405), PLGA (MESH:D000077182), Metal (MESH:D008670), anthracycline (MESH:D018943), folic acid (MESH:D005492), reactive oxygen species (MESH:D017382), perfluorooctyl bromide (MESH:C003072), VER (MESH:D014700), CS (MESH:D002586), Graphene oxide (MESH:C000628730), 90Y (MESH:C000615496), Chitosan (MESH:D048271), platinum (MESH:D010984), Aroplatin (MESH:C054367), quinone (MESH:C004532), CuS (MESH:C017846), CPT (MESH:D002166), nanogel (MESH:C413692), CPX-351 (MESH:C000629812), CYT-6091 (MESH:C000604550), ICG (MESH:D007208), OCT (MESH:D015282), amino acids (MESH:D000596), monoolein (MESH:C005953), CuI (MESH:C073870), docetaxel (MESH:D000077143), carbohydrates (MESH:D002241), HCPT (MESH:C120029), Au NPs (-), Vincristine (MESH:D014750), Depocyt (MESH:D003561), GA (MESH:D005708), tacrolimus (MESH:D016559), CUR (MESH:D003474), Glycyrrhetinic acid (MESH:D006034), poly(2-(diisopropyl amino)ethyl methacrylate) (MESH:C511861), phytantriol (MESH:C508873), Tetraphenylporphyrin (MESH:C409084), taxanes (MESH:D043823), tariquidar (MESH:C402343), water (MESH:D014867), poly(epsilon-caprolactone) (MESH:C016240), ATP (MESH:D000255), Fe2O3 (MESH:C000499), polylactide-co-glycolide (MESH:D011098), poly(2-(dimethylamino) ethyl methacrylate)-block-poly(2-(diisopropylamino) ethyl methacrylate) (MESH:C570790), Polymer (MESH:D011108), LEP-ETU (MESH:D017239), phospholipid (MESH:D010743) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Human immunodeficiency virus 1 (no rank) [taxon 11676] - **Mutations:** T34A - **Cell lines:** MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), PC3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035), 293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), KB-V1 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_2089), SK-MEL-3 — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_0550), SKOV-3TR — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_4V89), SKOV-3 — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532), GL261 — Mus musculus (Mouse), Mouse glioblastoma, Cancer cell line (CVCL_Y003), GBM319 — Homo sapiens (Human), Malignant neoplasm of multiple primary sites, Transformed cell line (CVCL_EQ08), A2780 — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_0134), pKH-rev — Homo sapiens (Human), Cleidocranial dysplasia, Induced pluripotent stem cell (CVCL_A4TS), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), MCF-7/ADR — Homo sapiens (Human), High grade ovarian serous adenocarcinoma, Cancer cell line (CVCL_1452), Hep3B — Homo sapiens (Human), Childhood hepatocellular carcinoma, Cancer cell line (CVCL_0326), A2780 ADR — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_1941), A431 — Homo sapiens (Human), Skin squamous cell carcinoma, Cancer cell line (CVCL_0037), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), Bel-7402 Liver cancer — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_5492), HUVEC — Homo sapiens (Human), Finite cell line (CVCL_2959), HepG-2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), K562 Leukemia — Homo sapiens (Human), Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_0004), AGS — Homo sapiens (Human), Gastric adenocarcinoma, Cancer cell line (CVCL_0139), SS37 — Homo sapiens (Human), Sickle cell disease, Induced pluripotent stem cell (CVCL_JW46), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), K7 — Mus musculus (Mouse), Mouse osteosarcoma, Cancer cell line (CVCL_W624), MDA-MD-453 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0418), CP20 — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_A5PS), B16F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045) ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9370272/full.md --- Source: https://tomesphere.com/paper/PMC9370272