Icebreaker-inspired Janus nanomotors to combat barriers in the delivery of chemotherapeutic agents
Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents. Herein, icebreaker-inspired Janus nanomotors (JMs) are developed to addres...
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| Veröffentlicht in: | Nanoscale 2021-04, Vol.13 (13), p.6545-6557 |
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| creator | Zhang, Zhanlin Zhang, Dandan Qiu, Bo Cao, Wenxiong Liu, Yuan Liu, Qingjie Li, Xiaohong |
| description | Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents. Herein, icebreaker-inspired Janus nanomotors (JMs) are developed to address these transportation barriers. Janus nanorods (JRs) are constructed
via
seed-defined growth of mesoporous silica nanoparticles on doxorubicin (DOX)-loaded hydroxyapatite (HAp) nanorods. One side of JRs is grafted with urease as the motion power
via
catalysis of physiologically existed urea, and hyaluronidase (HAase) is on the other side to digest the viscous extracellular matrices (ECM) of tumor tissues. The rod-like feature of JMs prolongs the blood circulation, and the self-propelling force and instantaneous digestion of hyaluronic acid along the moving paths promote extravasation across blood vessels and penetration in tumor mass, leading to 2-fold higher drug levels in tumors after JM administration than those with JRs. The digestion of ECM in the diffusion paths is more effective to enhance drug retention and diffusion in tumors compared with enzyme-mediated motion. The ECM digestion and motion capabilities of JMs show no influence on the endocytosis mechanism, but lead to over 3-fold higher cellular uptake than those of pristine JRs. The JM treatment promotes therapeutic efficacy in terms of survival prolongation, tumor growth inhibition and cell apoptosis induction and causes no tumor metastasis to lungs with normal alveolar spaces. Thus, the self-driven motion and instantaneous clearance of diffusion routes demonstrate a feasible strategy to combat a series of biological barriers in the delivery of chemotherapeutic agents in favor of antitumor efficacy.
Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents. |
| doi_str_mv | 10.1039/d0nr08853f |
| format | Article |
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via
seed-defined growth of mesoporous silica nanoparticles on doxorubicin (DOX)-loaded hydroxyapatite (HAp) nanorods. One side of JRs is grafted with urease as the motion power
via
catalysis of physiologically existed urea, and hyaluronidase (HAase) is on the other side to digest the viscous extracellular matrices (ECM) of tumor tissues. The rod-like feature of JMs prolongs the blood circulation, and the self-propelling force and instantaneous digestion of hyaluronic acid along the moving paths promote extravasation across blood vessels and penetration in tumor mass, leading to 2-fold higher drug levels in tumors after JM administration than those with JRs. The digestion of ECM in the diffusion paths is more effective to enhance drug retention and diffusion in tumors compared with enzyme-mediated motion. The ECM digestion and motion capabilities of JMs show no influence on the endocytosis mechanism, but lead to over 3-fold higher cellular uptake than those of pristine JRs. The JM treatment promotes therapeutic efficacy in terms of survival prolongation, tumor growth inhibition and cell apoptosis induction and causes no tumor metastasis to lungs with normal alveolar spaces. Thus, the self-driven motion and instantaneous clearance of diffusion routes demonstrate a feasible strategy to combat a series of biological barriers in the delivery of chemotherapeutic agents in favor of antitumor efficacy.
Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents.</description><identifier>ISSN: 2040-3364</identifier><identifier>EISSN: 2040-3372</identifier><identifier>DOI: 10.1039/d0nr08853f</identifier><identifier>PMID: 33885534</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Anticancer properties ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Blood circulation ; Blood vessels ; Cell Line, Tumor ; Diffusion ; Digestion ; Doxorubicin ; Drug Delivery Systems ; Hyaluronic acid ; Hydroxyapatite ; Icebreakers ; Nanoparticles ; Nanorods ; Nanotechnology devices ; Prolongation ; Silicon Dioxide ; Tumors</subject><ispartof>Nanoscale, 2021-04, Vol.13 (13), p.6545-6557</ispartof><rights>Copyright Royal Society of Chemistry 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-c24361288d12c8bbfd4397b65be82bcb4b6d19acc90e56cc71162152359952bf3</citedby><cites>FETCH-LOGICAL-c374t-c24361288d12c8bbfd4397b65be82bcb4b6d19acc90e56cc71162152359952bf3</cites><orcidid>0000-0003-1312-0215</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33885534$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Zhanlin</creatorcontrib><creatorcontrib>Zhang, Dandan</creatorcontrib><creatorcontrib>Qiu, Bo</creatorcontrib><creatorcontrib>Cao, Wenxiong</creatorcontrib><creatorcontrib>Liu, Yuan</creatorcontrib><creatorcontrib>Liu, Qingjie</creatorcontrib><creatorcontrib>Li, Xiaohong</creatorcontrib><title>Icebreaker-inspired Janus nanomotors to combat barriers in the delivery of chemotherapeutic agents</title><title>Nanoscale</title><addtitle>Nanoscale</addtitle><description>Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents. Herein, icebreaker-inspired Janus nanomotors (JMs) are developed to address these transportation barriers. Janus nanorods (JRs) are constructed
via
seed-defined growth of mesoporous silica nanoparticles on doxorubicin (DOX)-loaded hydroxyapatite (HAp) nanorods. One side of JRs is grafted with urease as the motion power
via
catalysis of physiologically existed urea, and hyaluronidase (HAase) is on the other side to digest the viscous extracellular matrices (ECM) of tumor tissues. The rod-like feature of JMs prolongs the blood circulation, and the self-propelling force and instantaneous digestion of hyaluronic acid along the moving paths promote extravasation across blood vessels and penetration in tumor mass, leading to 2-fold higher drug levels in tumors after JM administration than those with JRs. The digestion of ECM in the diffusion paths is more effective to enhance drug retention and diffusion in tumors compared with enzyme-mediated motion. The ECM digestion and motion capabilities of JMs show no influence on the endocytosis mechanism, but lead to over 3-fold higher cellular uptake than those of pristine JRs. The JM treatment promotes therapeutic efficacy in terms of survival prolongation, tumor growth inhibition and cell apoptosis induction and causes no tumor metastasis to lungs with normal alveolar spaces. Thus, the self-driven motion and instantaneous clearance of diffusion routes demonstrate a feasible strategy to combat a series of biological barriers in the delivery of chemotherapeutic agents in favor of antitumor efficacy.
Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents.</description><subject>Anticancer properties</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Blood circulation</subject><subject>Blood vessels</subject><subject>Cell Line, Tumor</subject><subject>Diffusion</subject><subject>Digestion</subject><subject>Doxorubicin</subject><subject>Drug Delivery Systems</subject><subject>Hyaluronic acid</subject><subject>Hydroxyapatite</subject><subject>Icebreakers</subject><subject>Nanoparticles</subject><subject>Nanorods</subject><subject>Nanotechnology devices</subject><subject>Prolongation</subject><subject>Silicon Dioxide</subject><subject>Tumors</subject><issn>2040-3364</issn><issn>2040-3372</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0c1LwzAYBvAgitPpxbsS8CJCNR9t2h5lOp0MBdFzSdK3rrNNZtIK--_N3JzgKSH58ZD3CUInlFxRwvPrkhhHsizh1Q46YCQmEecp293uRTxAh97PCRE5F3wfDTgPPOHxAVITDcqB_AAX1cYvagclfpSm99hIY1vbWedxZ7G2rZIdVtK5GsJRbXA3A1xCU3-BW2JbYT2D4Gfg5AL6rtZYvoPp_BHaq2Tj4XizDtHb-O519BBNn-8no5tppHkad5FmMReUZVlJmc6UqsqY56kSiYKMKa1iJUqaS61zAonQOqVUMJownuR5wlTFh-hinbtw9rMH3xVt7TU0jTRge1-whIosZIbBh-j8H53b3pnwupUihMaEpUFdrpV21nsHVbFwdSvdsqCkWDVf3JKnl5_mxwGfbSJ71UK5pb9VB3C6Bs7r7e3f1_FvaRaIcA</recordid><startdate>20210407</startdate><enddate>20210407</enddate><creator>Zhang, Zhanlin</creator><creator>Zhang, Dandan</creator><creator>Qiu, Bo</creator><creator>Cao, Wenxiong</creator><creator>Liu, Yuan</creator><creator>Liu, Qingjie</creator><creator>Li, Xiaohong</creator><general>Royal Society of Chemistry</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1312-0215</orcidid></search><sort><creationdate>20210407</creationdate><title>Icebreaker-inspired Janus nanomotors to combat barriers in the delivery of chemotherapeutic agents</title><author>Zhang, Zhanlin ; Zhang, Dandan ; Qiu, Bo ; Cao, Wenxiong ; Liu, Yuan ; Liu, Qingjie ; Li, Xiaohong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-c24361288d12c8bbfd4397b65be82bcb4b6d19acc90e56cc71162152359952bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anticancer properties</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>Blood circulation</topic><topic>Blood vessels</topic><topic>Cell Line, Tumor</topic><topic>Diffusion</topic><topic>Digestion</topic><topic>Doxorubicin</topic><topic>Drug Delivery Systems</topic><topic>Hyaluronic acid</topic><topic>Hydroxyapatite</topic><topic>Icebreakers</topic><topic>Nanoparticles</topic><topic>Nanorods</topic><topic>Nanotechnology devices</topic><topic>Prolongation</topic><topic>Silicon Dioxide</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Zhanlin</creatorcontrib><creatorcontrib>Zhang, Dandan</creatorcontrib><creatorcontrib>Qiu, Bo</creatorcontrib><creatorcontrib>Cao, Wenxiong</creatorcontrib><creatorcontrib>Liu, Yuan</creatorcontrib><creatorcontrib>Liu, Qingjie</creatorcontrib><creatorcontrib>Li, Xiaohong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Nanoscale</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Zhanlin</au><au>Zhang, Dandan</au><au>Qiu, Bo</au><au>Cao, Wenxiong</au><au>Liu, Yuan</au><au>Liu, Qingjie</au><au>Li, Xiaohong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Icebreaker-inspired Janus nanomotors to combat barriers in the delivery of chemotherapeutic agents</atitle><jtitle>Nanoscale</jtitle><addtitle>Nanoscale</addtitle><date>2021-04-07</date><risdate>2021</risdate><volume>13</volume><issue>13</issue><spage>6545</spage><epage>6557</epage><pages>6545-6557</pages><issn>2040-3364</issn><eissn>2040-3372</eissn><abstract>Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents. Herein, icebreaker-inspired Janus nanomotors (JMs) are developed to address these transportation barriers. Janus nanorods (JRs) are constructed
via
seed-defined growth of mesoporous silica nanoparticles on doxorubicin (DOX)-loaded hydroxyapatite (HAp) nanorods. One side of JRs is grafted with urease as the motion power
via
catalysis of physiologically existed urea, and hyaluronidase (HAase) is on the other side to digest the viscous extracellular matrices (ECM) of tumor tissues. The rod-like feature of JMs prolongs the blood circulation, and the self-propelling force and instantaneous digestion of hyaluronic acid along the moving paths promote extravasation across blood vessels and penetration in tumor mass, leading to 2-fold higher drug levels in tumors after JM administration than those with JRs. The digestion of ECM in the diffusion paths is more effective to enhance drug retention and diffusion in tumors compared with enzyme-mediated motion. The ECM digestion and motion capabilities of JMs show no influence on the endocytosis mechanism, but lead to over 3-fold higher cellular uptake than those of pristine JRs. The JM treatment promotes therapeutic efficacy in terms of survival prolongation, tumor growth inhibition and cell apoptosis induction and causes no tumor metastasis to lungs with normal alveolar spaces. Thus, the self-driven motion and instantaneous clearance of diffusion routes demonstrate a feasible strategy to combat a series of biological barriers in the delivery of chemotherapeutic agents in favor of antitumor efficacy.
Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>33885534</pmid><doi>10.1039/d0nr08853f</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-1312-0215</orcidid></addata></record> |
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| subjects | Anticancer properties Antineoplastic Agents - therapeutic use Apoptosis Blood circulation Blood vessels Cell Line, Tumor Diffusion Digestion Doxorubicin Drug Delivery Systems Hyaluronic acid Hydroxyapatite Icebreakers Nanoparticles Nanorods Nanotechnology devices Prolongation Silicon Dioxide Tumors |
| title | Icebreaker-inspired Janus nanomotors to combat barriers in the delivery of chemotherapeutic agents |
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