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Surgical resection and ablation therapy have limited efficacy for patients with advanced HCC and poor liver function, so pharmacotherapy is the first-line option for those patients. Traditional antitumor drugs have the disadvantages of poor biological distribution and pharmacokinetics, poor target selectivity, high resistance, and high toxicity to nontargeted tissues. Recently, the development of nanotechnology has significantly improved drug delivery to tumor sites by changing the physical and biological characteristics of drugs and nanocarriers to improve their pharmacokinetics and biological distribution and to selectively accumulate cytotoxic agents at tumor sites. Here, we systematically review the tumor microenvironment of HCC and the recent application of nanotechnology in HCC.<\/jats:p>","DOI":"10.1186\/s12964-021-00796-x","type":"journal-article","created":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T13:02:43Z","timestamp":1646485363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Drug delivery strategy in hepatocellular carcinoma therapy"],"prefix":"10.1186","volume":"20","author":[{"given":"Sisi","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengwei","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanqiu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwen","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifang","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0766-8794","authenticated-orcid":false,"given":"Chengbo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,5]]},"reference":[{"issue":"5","key":"796_CR1","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","volume":"136","author":"J Ferlay","year":"2015","unstructured":"Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. 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