# Recent Advances in Improved Anticancer Efficacies of Camptothecin Nano-Formulations: A Systematic Review

**Authors:** Maryam Ghanbari-Movahed, Tea Kaceli, Arijit Mondal, Mohammad Hosein Farzaei, Anupam Bishayee

PMC · DOI: 10.3390/biomedicines9050480 · Biomedicines · 2021-04-27

## TL;DR

This review explores how nano-formulations of Camptothecin improve its anticancer effectiveness by overcoming its solubility and stability issues.

## Contribution

The paper systematically evaluates the enhanced antitumor activity of Camptothecin nano-formulations compared to free CPT.

## Key findings

- CPT nano-formulations show higher antitumor activity than free CPT in various cancers.
- Nano-formulations improve CPT's solubility and bioavailability, enhancing its therapeutic potential.
- The study supports the clinical application of CPT nano-formulations for future cancer treatments.

## Abstract

Camptothecin (CPT), a natural plant alkaloid, has indicated potent antitumor activities via targeting intracellular topoisomerase I. The promise that CPT holds in therapies is restricted through factors that include lactone ring instability and water insolubility, which limits the drug oral solubility and bioavailability in blood plasma. Novel strategies involving CPT pharmacological and low doses combined with nanoparticles have indicated potent anticancer activity in vitro and in vivo. This systematic review aims to provide a comprehensive and critical evaluation of the anticancer ability of nano-CPT in various cancers as a novel and more efficient natural compound for drug development. Studies were identified through systematic searches of PubMed, Scopus, and ScienceDirect. Eligibility checks were performed based on predefined selection criteria. Eighty-two papers were included in this systematic review. There was strong evidence for the association between antitumor activity and CPT treatment. Furthermore, studies indicated that CPT nano-formulations have higher antitumor activity in comparison to free CPT, which results in enhanced efficacy for cancer treatment. The results of our study indicate that CPT nano-formulations are a potent candidate for cancer treatment and may provide further support for the clinical application of natural antitumor agents with passive targeting of tumors in the future.

## Linked entities

- **Chemicals:** Camptothecin (PubChem CID 2538)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, CDC25C (cell division cycle 25C) [NCBI Gene 995] {aka CDC25, PPP1R60}, Mofp2 (mesenteric and omental fat pad weight 2) [NCBI Gene 100035475] {aka Mof2}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CHEK2 (checkpoint kinase 2) [NCBI Gene 11200] {aka CDS1, CHK2, HuCds1, LFS2, PP1425, RAD53}
- **Diseases:** CRC (MESH:D015179), Gliomas (MESH:D005910), Melanoma (MESH:D008545), retardation (MESH:D008607), PDA (MESH:D004374), Prostate Cancer (MESH:D011471), Lung Cancer (MESH:D008175), B16 tumor (MESH:D008546), death (MESH:D003643), Toxicity (MESH:D064420), HCC (MESH:D006528), bladder, brain, breast, cervical, colon (MESH:D061325), Skin Cancer (MESH:D012878), Brain Cancer (MESH:D001932), Ovarian Cancer (MESH:D010051), leukemia (MESH:D007938), inflammation (MESH:D007249), metastasis (MESH:D009362), Pancreatic Cancer (MESH:D010190), MDA-MB-231BO (OMIM:613675), Bladder Cancer (MESH:D001749), C6 glioma (MESH:C567307), EAC (MESH:D002286), Necrosis (MESH:D009336), liver, lung (MESH:D008107), LLC tumor (MESH:D009369), female reproductive system tumors (MESH:D060737), Breast Cancer (MESH:D001943), colon tumor (MESH:D003110), Cervical Cancer (MESH:D002583)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Camptotheca acuminata (species) [taxon 16922], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** B16 tumor — Mus musculus (Mouse), Hybridoma (CVCL_U043), GL261-luc2 — Mus musculus (Mouse), Mouse glioblastoma, Cancer cell line (CVCL_X986), HCT 116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), SKOV3 — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), C6 tumor — Rattus norvegicus (Rat), Rat malignant glioma, Cancer cell line (CVCL_0194), U14 — Mus musculus (Mouse), Mouse cervical carcinoma, Cancer cell line (CVCL_9U56), HCT-8 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_2478), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), BT-474 tumor — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0179), EMT6 tumor — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_1923), C26 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0507), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), HT-29.Fluc — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_5J00), MIA PaCa-2 — Homo sapiens (Human), Pancreatic undifferentiated carcinoma, Cancer cell line (CVCL_0428), LLC — Mus musculus (Mouse), Malignant tumors of the mouse pulmonary system, Cancer cell line (CVCL_5653), DU145 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0105), LoVo — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0399), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), AY27 — Rattus norvegicus (Rat), Transitional cell carcinoma of the rat urinary bladder, Cancer cell line (CVCL_S825), NCI-H460 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_0459), R2SC — Homo sapiens (Human), Embryonic stem cell (CVCL_6F20), Breast 4T1 — Homo sapiens (Human), Anaplastic large cell lymphoma, ALK-negative, Cancer cell line (CVCL_A1FA), 9L — Rattus norvegicus (Rat), Rat malignant glioma, Cancer cell line (CVCL_1928), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), GL261 — Mus musculus (Mouse), Mouse glioblastoma, Cancer cell line (CVCL_Y003), MDA — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_4747), PANC-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), SW620 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0547), Hep1- — Homo sapiens (Human), Cervical carcinoma, Cancer cell line (CVCL_JB76), BxPC-3 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0186), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), BEL-7402 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_5492), H22 — Homo sapiens (Human), Peripheral primitive neuroectodermal tumor of bone, Cancer cell line (CVCL_1E32), Breast — Homo sapiens (Human), Transformed cell line (CVCL_WC49), U-87 MG — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022)

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8146681/full.md

## References

158 references — full list in the complete paper: https://tomesphere.com/paper/PMC8146681/full.md

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Source: https://tomesphere.com/paper/PMC8146681