# Advances in Polymer Micelles for Cancer Therapy: From Conventional to Smart Delivery Systems **Authors:** Rayna Georgieva Bryaskova, Krasimir Georgiev Staykov, Damyan Stoyanov Ganchev PMC · DOI: 10.3390/pharmaceutics18020177 · 2026-01-29 ## TL;DR Polymeric micelles are being developed as smart drug delivery systems for cancer, improving drug solubility, targeting, and reducing toxicity. ## Contribution This review highlights the transition from conventional to smart polymer micelles for more precise and effective cancer therapy. ## Key findings - Conventional PEG-based micelles use the EPR effect for passive tumor targeting. - Smart micelles respond to stimuli for controlled drug release and improved therapeutic effectiveness. - Recent advancements include new polymer designs and targeting strategies reaching clinical stages. ## Abstract Polymeric micelles have become a versatile and clinically significant class of nanocarriers for cancer therapy. They effectively solubilize poorly water-soluble anticancer drugs, extend their circulation in the bloodstream, and promote accumulation in tumors. Early studies focused on conventional PEG-based polymeric micelles that utilize passive targeting based on the enhanced permeability and retention (EPR) effect, with several of these advancing to clinical trials. Active targeting strategies using modified polymer micelles with various targeting ligands have been introduced to enhance cellular uptake and improve tumor specificity. Recently, the field has shifted toward smart polymer micelles that can respond to both internal (endogenous) and external (exogenous) stimuli. These stimuli-responsive systems enable controlled drug release, enhance delivery inside cells, and improve therapeutic effectiveness, all while reducing systemic toxicity. This review summarizes recent advancements in polymer design, drug-loading techniques, preparation methods, and targeting strategies for polymeric micelles, highlighting both preclinical progress and systems that have reached clinical stages. The transition from conventional to smart polymer micelles is a significant advancement toward achieving more precise, effective, and personalized cancer nanomedicine. ## Linked entities - **Diseases:** cancer (MONDO:0004992) ## Full-text entities - **Genes:** BCL2L1 (BCL2 like 1) [NCBI Gene 598] {aka BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, ITGAV (integrin subunit alpha V) [NCBI Gene 3685] {aka CD51, IDNDC, MSK8, VNRA, VTNR}, TFRC (transferrin receptor) [NCBI Gene 7037] {aka CD71, IMD46, T9, TFR, TFR1, TR}, TOP2A (DNA topoisomerase II alpha) [NCBI Gene 7153] {aka TOP2, TOP2alpha, TOPIIA, TP2A}, KLK3 (kallikrein related peptidase 3) [NCBI Gene 354] {aka APS, KLK2A1, PSA, hK3}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, TNFSF10 (TNF superfamily member 10) [NCBI Gene 8743] {aka APO2L, Apo-2L, CD253, TANCR, TL2, TNLG6A}, TNFRSF10B (TNF receptor superfamily member 10b) [NCBI Gene 8795] {aka CD262, DR5, KILLER, KILLER/DR5, TRAIL-R2, TRAILR2}, FOLH1 (folate hydrolase 1) [NCBI Gene 2346] {aka FGCP, FOLH, GCP2, GCPII, NAALAD1, PSM}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG} - **Diseases:** leukemia (MESH:D007938), colon cancer (MESH:D015179), death (MESH:D003643), breast and ovarian cancers (MESH:D061325), neutropenia (MESH:D009503), bone metastasis (MESH:D009362), epidermal carcinoma (MESH:D004814), anemia (MESH:D000740), stomatitis (MESH:D013280), ototoxicity (MESH:D006311), Cytotoxicity (MESH:D064420), weight loss (MESH:D015431), thrombocytopenia (MESH:D013921), Lewis lung carcinoma (MESH:D018827), hypersensitivity (MESH:D004342), breast, ovarian, and prostate cancers (MESH:D010051), peripheral neuropathy (MESH:D010523), endometrial stromal sarcoma (MESH:D018203), breast adenocarcinoma (MESH:D001943), lymphoma (MESH:D008223), febrile neutropenia (MESH:D064147), solid (MESH:D018250), Neuropathy (MESH:D009422), glioblastoma (MESH:D005909), DLTs (MESH:D045745), necrosis (MESH:D009336), HCC (MESH:D006528), multidrug (MESH:D018088), pancreatic adenocarcinoma (MESH:D010190), B16 (MESH:D008546), uterine cervix cancer (MESH:D002583), small cell lung cancer (MESH:D055752), prostate cancer (MESH:D011471), melanoma (MESH:D008545), glioma (MESH:D005910), CMC (MESH:D016638), injury to (MESH:D014947), lung infection (MESH:D012141), osteosarcoma (MESH:D012516), DL (MESH:C537113), breast, lung, esophageal, prostate, bladder, head, and neck cancers (MESH:D006258), adenocarcinoma (MESH:D000230), Tumor (MESH:D009369), neurotoxicity (MESH:D020258), lung cancer (MESH:D008175), myelomas (MESH:D009101), diarrhea (MESH:D003967), fatigue (MESH:D005221), nausea (MESH:D009325), gastric cancer (MESH:D013274), alopecia (MESH:D000505), mammary carcinoma tumor (MESH:D015674), leukopenia (MESH:D007970), non (MESH:C580335), colon adenocarcinoma (MESH:D003110), oral epidermoid carcinoma (MESH:D002294), KB (OMIM:300845), NSCLC (MESH:D002289), angiosarcoma (MESH:D006394), soft-tissue sarcoma (MESH:D012509) - **Chemicals:** RGD (MESH:C047981), oximes (MESH:D010091), disulfide (MESH:D004220), D-alpha-tocopheryl polyethylene glycol 1000 succinate (MESH:C014225), Adriamycin (MESH:D004317), NK105 (MESH:C500671), vinyl ethers (MESH:C100195), Pluronic (MESH:D020442), CUR (MESH:D003474), helium (MESH:D006371), PDLL (-), Cisplatin (MESH:D002945), IR780 (MESH:C548458), ethyl acetate (MESH:C007650), EPI (MESH:D015251), NC 6004 (MESH:C557897), oil (MESH:D009821), Pluronic P123 (MESH:C464484), tert-butanol (MESH:D020002), poly(N-vinylpyrrolidone)-b-poly(epsilon-caprolactone) (MESH:C550000), PCL (MESH:C016240), CL (MESH:D002713), NH2 (MESH:D000588), hydroxyapatite (MESH:D017886), F127 (MESH:C078661), PSI (MESH:C025252), MTT (MESH:C070243), HMAAm (MESH:C066443), thiol (MESH:D013438), Tet (MESH:C009438), Pluronic P105 (MESH:C519610), levulinic acid (MESH:C032246), trifluoromethane (MESH:C009554), purine (MESH:C030985), -poly(d,l-lactide) (MESH:C033616), lactone (MESH:D007783), Taxanes (MESH:D043823), lipids (MESH:D008055), ALN (MESH:D019386), PEG-b-poly(epsilon-caprolactone) (MESH:C476300), GSH (MESH:D005978), carbon dioxide (MESH:D002245), lactide (MESH:C091880), propane (MESH:D011407), nitroxide (MESH:C039900), maleimide (MESH:C043592), Genexol-PM (MESH:C000708971), polyphenol (MESH:D059808), ATP (MESH:D000255), TRITC (MESH:C009434), propylene oxide (MESH:C009068), NK911 (MESH:C438847), N-vinylpyrrolidone (MESH:C042670), ROS (MESH:D017382), FA (MESH:D005492), BIND-014 (MESH:D000077143), PAE (MESH:C507253), Cremophor EL (MESH:C000515), Poly(2-(diisopropylamino) ethyl methacrylate (MESH:C511861), DP (MESH:D004176) - **Species:** Danio rerio (leopard danio, species) [taxon 7955], Botryodiscia tetrandra (species) [taxon 425106], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090] - **Cell lines:** C-26 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0507), EMT-6 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_1923), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), MDA MB 231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), BGC 823 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_3360), H661 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_1577), K7 — Mus musculus (Mouse), Mouse osteosarcoma, Cancer cell line (CVCL_W624), Huh7 — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_0336), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), KB — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0372), JE6.1 — Mus musculus (Mouse), Transformed cell line (CVCL_VH02), MATB III — Rattus norvegicus (Rat), Rat malignant mesothelioma, Cancer cell line (CVCL_C7S0), U87 glioblastoma — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022), SLK — Homo sapiens (Human), Clear cell renal cell carcinoma, Cancer cell line (CVCL_9569), PANC-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), Dalton's lymphoma — Mus musculus (Mouse), Hybridoma (CVCL_U609), H22 — Homo sapiens (Human), Peripheral primitive neuroectodermal tumor of bone, Cancer cell line (CVCL_1E32), BT-474 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0179), T98G. — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0556), OVCAR-3 — Homo sapiens (Human), High grade ovarian serous adenocarcinoma, Cancer cell line (CVCL_0465), PC3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035), LNCaP — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0395), SK-OV-3 — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532), A2780 — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_0134), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), CRL 2429 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_ZA05), B16 — Mus musculus (Mouse), Hybridoma (CVCL_U043), /c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103), MIA PaCa-2 — Homo sapiens (Human), Pancreatic undifferentiated carcinoma, Cancer cell line (CVCL_0428), BXPC3 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0186), KBv — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_D599), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), Raji — Homo sapiens (Human), EBV-related Burkitt lymphoma, Cancer cell line (CVCL_0511), A-549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), M109 — Mus musculus (Mouse), Malignant tumors of the mouse pulmonary system, Cancer cell line (CVCL_H602), MDA-MB-468 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0419), HeLa-Luc — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_5J41), SGC7901 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0520), CCL-110 — Mus musculus (Mouse), Undefined cell line type (CVCL_M023), MCF-7/ADR — Homo sapiens (Human), High grade ovarian serous adenocarcinoma, Cancer cell line (CVCL_1452), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), B16F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159), ZR-75-1 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0588), DL — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z231), CT26 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_7254), RKO — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0504), C6 — Rattus norvegicus (Rat), Rat malignant glioma, Cancer cell line (CVCL_0194), Hep3B — Homo sapiens (Human), Childhood hepatocellular carcinoma, Cancer cell line (CVCL_0326), K-562 — Homo sapiens (Human), Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_0004), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031) ## Figures 8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12944056/full.md --- Source: https://tomesphere.com/paper/PMC12944056