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The low immunogenicity and non-toxicity of collagen-NPs makes it preferable for a wide range of applications. A total of eight morphologically distinct actinomycetes strains were newly isolated from various soil samples in Egypt. The cell-free supernatants of these strains were tested for their ability. These strains' cell-free supernatants were tested for their ability to synthesize collagen-NPs. Five isolates had the ability to biosynthesize collagen-NPs. Among these, a potential culture,\n                    <jats:italic>Streptomyces<\/jats:italic>\n                    sp. NEAA-1, was chosen and identified as\n                    <jats:italic>Streptomyces xinghaiensis<\/jats:italic>\n                    NEAA-1 based on 16S rRNA sequence analysis as well as morphological, cultural and physiological properties. The sequence data has been deposited at the GenBank database under the accession No. OQ652077.1. Face-centered central composite design (FCCD) has been conducted to maximize collagen-NPs biosynthesis. Maximum collagen-NPs was 8.92\u00a0mg\/mL under the condition of 10\u00a0mg\/mL of collagen concentration, initial pH 7, incubation time of 48\u00a0h and temperature of 35\u00a0\u00b0C. The yield of collagen-NPs obtained via FCCD optimization (8.92\u00a0mg\/mL) was 3.32-fold compared to the yield obtained under non-optimized conditions (2.5\u00a0mg\/mL). TEM analysis of collagen-NPs showed hollow sphere nanoscale particles with mean of 32.63\u2009\u00b1\u200914.59\u00a0nm in diameter. FTIR spectra showed major peaks of amide I, amide II and amide III of collagen and also the cell-free supernatant involved in effective capping of collagen-NPs. The biosynthesized collagen-NPs exhibited anti-hemolytic, antioxidant and cytotoxic activities. The inhibitory concentrations (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) against MCF-7, HeP-G2 and HCT116 cell lines were 11.62\u2009\u00b1\u20090.8, 19.60\u2009\u00b1\u20091.2 and 41.67\u2009\u00b1\u20092.2\u00a0\u00b5g\/mL; respectively. The\n                    <jats:italic>in-vivo<\/jats:italic>\n                    investigation showed that collagen-NPs can suppress Ehrlich ascites carcinoma (EAC) growth in mice. The collagen-NPs\/DOX combination treatment showed considerable tumor growth suppression (95.58%). Collagen-NPs evaluated as nanocarrier with a chemotherapeutic agent, methotrexate (MTX). The average size of MTX loaded collagen-NPs was 42.73\u2009\u00b1\u20093.5\u00a0nm. Encapsulation efficiency percentage (EE %) was 48.91% and drug loading percentage (DL %) was 24.45%.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-53342-3","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T11:05:09Z","timestamp":1707390309000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Green synthesis of collagen nanoparticles by Streptomyces xinghaiensis NEAA-1, statistical optimization, characterization, and evaluation of their anticancer potential"],"prefix":"10.1038","volume":"14","author":[{"given":"Asmaa A.","family":"El-Sawah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-9194","authenticated-orcid":false,"given":"Noura El-Ahmady","family":"El-Naggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba E.","family":"Eldegla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda M.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"53342_CR1","doi-asserted-by":"publisher","first-page":"1155622","DOI":"10.3389\/fmicb.2023.1155622","volume":"14","author":"KA Altammar","year":"2023","unstructured":"Altammar, K. 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