Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope
Identifieur interne : 000C45 ( Ncbi/Merge ); précédent : 000C44; suivant : 000C46Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope
Auteurs : Lucia Salvioni ; Maria Antonietta Rizzuto ; Jessica Armida Bertolini ; Laura Pandolfi ; Miriam Colombo ; Davide Prosperi [Italie]Source :
- Cancers [ 2072-6694 ] ; 2019.
Abstract
Starting with the enhanced permeability and retention (EPR) effect discovery, nanomedicine has gained a crucial role in cancer treatment. The advances in the field have led to the approval of nanodrugs with improved safety profile and still inspire the ongoing investigations. However, several restrictions, such as high manufacturing costs, technical challenges, and effectiveness below expectations, raised skeptical opinions within the scientific community about the clinical relevance of nanomedicine. In this review, we aim to give an overall vision of the current hurdles encountered by nanotherapeutics along with their design, development, and translation, and we offer a prospective view on possible strategies to overcome such limitations.
Url:
DOI: 10.3390/cancers11121855
PubMed: 31769416
PubMed Central: 6966668
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PMC:6966668Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope</title><author><name sortKey="Salvioni, Lucia" sort="Salvioni, Lucia" uniqKey="Salvioni L" first="Lucia" last="Salvioni">Lucia Salvioni</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation></author><author><name sortKey="Rizzuto, Maria Antonietta" sort="Rizzuto, Maria Antonietta" uniqKey="Rizzuto M" first="Maria Antonietta" last="Rizzuto">Maria Antonietta Rizzuto</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation></author><author><name sortKey="Bertolini, Jessica Armida" sort="Bertolini, Jessica Armida" uniqKey="Bertolini J" first="Jessica Armida" last="Bertolini">Jessica Armida Bertolini</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation></author><author><name sortKey="Pandolfi, Laura" sort="Pandolfi, Laura" uniqKey="Pandolfi L" first="Laura" last="Pandolfi">Laura Pandolfi</name><affiliation><nlm:aff id="af2-cancers-11-01855">Unit of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy;<email>l.pandolfi@smatteo.pv.it</email></nlm:aff></affiliation></author><author><name sortKey="Colombo, Miriam" sort="Colombo, Miriam" uniqKey="Colombo M" first="Miriam" last="Colombo">Miriam Colombo</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation></author><author><name sortKey="Prosperi, Davide" sort="Prosperi, Davide" uniqKey="Prosperi D" first="Davide" last="Prosperi">Davide Prosperi</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-cancers-11-01855">Nanomedicine Laboratory, ICS Maugeri, via S. Maugeri 10, 27100 Pavia, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Nanomedicine Laboratory, ICS Maugeri, via S. Maugeri 10, 27100 Pavia</wicri:regionArea><wicri:noRegion>27100 Pavia</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31769416</idno><idno type="pmc">6966668</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966668</idno><idno type="RBID">PMC:6966668</idno><idno type="doi">10.3390/cancers11121855</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000907</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000907</idno><idno type="wicri:Area/Pmc/Curation">000907</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000907</idno><idno type="wicri:Area/Pmc/Checkpoint">000288</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000288</idno><idno type="wicri:Area/Ncbi/Merge">000C45</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope</title><author><name sortKey="Salvioni, Lucia" sort="Salvioni, Lucia" uniqKey="Salvioni L" first="Lucia" last="Salvioni">Lucia Salvioni</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation></author><author><name sortKey="Rizzuto, Maria Antonietta" sort="Rizzuto, Maria Antonietta" uniqKey="Rizzuto M" first="Maria Antonietta" last="Rizzuto">Maria Antonietta Rizzuto</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation></author><author><name sortKey="Bertolini, Jessica Armida" sort="Bertolini, Jessica Armida" uniqKey="Bertolini J" first="Jessica Armida" last="Bertolini">Jessica Armida Bertolini</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation></author><author><name sortKey="Pandolfi, Laura" sort="Pandolfi, Laura" uniqKey="Pandolfi L" first="Laura" last="Pandolfi">Laura Pandolfi</name><affiliation><nlm:aff id="af2-cancers-11-01855">Unit of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy;<email>l.pandolfi@smatteo.pv.it</email></nlm:aff></affiliation></author><author><name sortKey="Colombo, Miriam" sort="Colombo, Miriam" uniqKey="Colombo M" first="Miriam" last="Colombo">Miriam Colombo</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation></author><author><name sortKey="Prosperi, Davide" sort="Prosperi, Davide" uniqKey="Prosperi D" first="Davide" last="Prosperi">Davide Prosperi</name><affiliation><nlm:aff id="af1-cancers-11-01855">Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-cancers-11-01855">Nanomedicine Laboratory, ICS Maugeri, via S. Maugeri 10, 27100 Pavia, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Nanomedicine Laboratory, ICS Maugeri, via S. Maugeri 10, 27100 Pavia</wicri:regionArea><wicri:noRegion>27100 Pavia</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cancers</title><idno type="eISSN">2072-6694</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Starting with the enhanced permeability and retention (EPR) effect discovery, nanomedicine has gained a crucial role in cancer treatment. The advances in the field have led to the approval of nanodrugs with improved safety profile and still inspire the ongoing investigations. However, several restrictions, such as high manufacturing costs, technical challenges, and effectiveness below expectations, raised skeptical opinions within the scientific community about the clinical relevance of nanomedicine. In this review, we aim to give an overall vision of the current hurdles encountered by nanotherapeutics along with their design, development, and translation, and we offer a prospective view on possible strategies to overcome such limitations.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Feynman, R P" uniqKey="Feynman R">R.P. Feynman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tibbals, H F" uniqKey="Tibbals H">H.F. Tibbals</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Etheridge, M L" uniqKey="Etheridge M">M.L. Etheridge</name></author><author><name sortKey="Campbell, S A" uniqKey="Campbell S">S.A. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cancers (Basel)</journal-id><journal-id journal-id-type="iso-abbrev">Cancers (Basel)</journal-id><journal-id journal-id-type="publisher-id">cancers</journal-id><journal-title-group><journal-title>Cancers</journal-title></journal-title-group><issn pub-type="epub">2072-6694</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31769416</article-id><article-id pub-id-type="pmc">6966668</article-id><article-id pub-id-type="doi">10.3390/cancers11121855</article-id><article-id pub-id-type="publisher-id">cancers-11-01855</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Salvioni</surname><given-names>Lucia</given-names></name><xref ref-type="aff" rid="af1-cancers-11-01855">1</xref><xref ref-type="author-notes" rid="fn1-cancers-11-01855">†</xref></contrib><contrib contrib-type="author"><name><surname>Rizzuto</surname><given-names>Maria Antonietta</given-names></name><xref ref-type="aff" rid="af1-cancers-11-01855">1</xref><xref ref-type="author-notes" rid="fn1-cancers-11-01855">†</xref></contrib><contrib contrib-type="author"><name><surname>Bertolini</surname><given-names>Jessica Armida</given-names></name><xref ref-type="aff" rid="af1-cancers-11-01855">1</xref></contrib><contrib contrib-type="author"><name><surname>Pandolfi</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="af2-cancers-11-01855">2</xref></contrib><contrib contrib-type="author"><name><surname>Colombo</surname><given-names>Miriam</given-names></name><xref ref-type="aff" rid="af1-cancers-11-01855">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-4577-9575</contrib-id><name><surname>Prosperi</surname><given-names>Davide</given-names></name><xref ref-type="aff" rid="af1-cancers-11-01855">1</xref><xref ref-type="aff" rid="af3-cancers-11-01855">3</xref><xref rid="c1-cancers-11-01855" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-cancers-11-01855"><label>1</label>Department of Biotecnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy;<email>lucia.salvioni@unimib.it</email> (L.S.);<email>maria.rizzuto@unimib.it</email> (M.A.R.);<email>jessica.bertolini@unimib.it</email> (J.A.B.);<email>miriam.colombo@unimib.it</email> (M.C.)</aff><aff id="af2-cancers-11-01855"><label>2</label>Unit of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy;<email>l.pandolfi@smatteo.pv.it</email></aff><aff id="af3-cancers-11-01855"><label>3</label>Nanomedicine Laboratory, ICS Maugeri, via S. Maugeri 10, 27100 Pavia, Italy</aff><author-notes><corresp id="c1-cancers-11-01855"><label>*</label>Correspondence: <email>davide.prosperi@unimib.it</email></corresp><fn id="fn1-cancers-11-01855"><label>†</label><p>These authors contributed equally to this paper.</p></fn></author-notes><pub-date pub-type="epub"><day>25</day><month>11</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>12</month><year>2019</year></pub-date><volume>11</volume><issue>12</issue><elocation-id>1855</elocation-id><history><date date-type="received"><day>31</day><month>10</month><year>2019</year></date><date date-type="accepted"><day>22</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Starting with the enhanced permeability and retention (EPR) effect discovery, nanomedicine has gained a crucial role in cancer treatment. The advances in the field have led to the approval of nanodrugs with improved safety profile and still inspire the ongoing investigations. However, several restrictions, such as high manufacturing costs, technical challenges, and effectiveness below expectations, raised skeptical opinions within the scientific community about the clinical relevance of nanomedicine. In this review, we aim to give an overall vision of the current hurdles encountered by nanotherapeutics along with their design, development, and translation, and we offer a prospective view on possible strategies to overcome such limitations.</p></abstract><kwd-group><kwd>cancer nanomedicine</kwd><kwd>EPR effect</kwd><kwd>tumor microenvironment</kwd><kwd>nanoparticles</kwd><kwd>nano–bio interactions</kwd><kwd>clinical translation</kwd></kwd-group></article-meta></front><floats-group><fig id="cancers-11-01855-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Tunable physical and chemical properties of nanocarriers (NCs).</p></caption><graphic xlink:href="cancers-11-01855-g001"></graphic></fig><fig id="cancers-11-01855-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Tumor microenvironment. Tumor tissue is characterized by a high cellular density that hampers oxygen and nutrient perfusion. Accordingly, cancer cells are genetically and epigenetically heterogeneous, and those located far from the blood vessels: (1) favor an anaerobic metabolism that leads to the environment acidification; (2) are more resistant to pharmacological treatments because of their low division rate and genetic instability [<xref rid="B42-cancers-11-01855" ref-type="bibr">42</xref>]. Fibroblasts and pericytes are responsible for tissue remodeling, while the immunosuppressive milieu hinders immune cell activity. NCs extravasation and penetration are mainly limited by solid stress and high interstitial fluid pressure, which in certain areas may reach values close to the aortic pressure [<xref rid="B43-cancers-11-01855" ref-type="bibr">43</xref>].</p></caption><graphic xlink:href="cancers-11-01855-g002"></graphic></fig><fig id="cancers-11-01855-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>(<bold>A</bold>) Publication peak of “nanoparticles” related papers; (<bold>B</bold>) Subject areas of “nanoparticles + cancer” papers. Elaborated data are derived from the Scopus research tool.</p></caption><graphic xlink:href="cancers-11-01855-g003"></graphic></fig><table-wrap id="cancers-11-01855-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">cancers-11-01855-t001_Table 1</object-id><label>Table 1</label><caption><p>Properties-dependent clearance of nanocarriers (NCs).</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Biodistribution Profiles in Clearance Organs</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">SIZE</td><td align="left" valign="middle" rowspan="1" colspan="1">Renal excretion is particularly relevant for NCs below the threshold value (ca. 5.5 nm) [<xref rid="B25-cancers-11-01855" ref-type="bibr">25</xref>].<break></break>MPS clearance is operated by liver>spleen>lung phagocytes. However, the spleen and lung fraction increase with the particle size: NCs > 150 nm are more prone to splenic filtration, while lung accumulation is particularly promoted when the NCs size is close to the micromillimeter range, or they aggregate [<xref rid="B26-cancers-11-01855" ref-type="bibr">26</xref>,<xref rid="B27-cancers-11-01855" ref-type="bibr">27</xref>].</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">SURFACE CHARGE</td><td align="left" valign="middle" rowspan="1" colspan="1">It is generally accepted that positively charged NCs are more rapidly sequestered by MPS than negative and neutral NCs due to the highly-dense coating of serum proteins formed on the administration [<xref rid="B27-cancers-11-01855" ref-type="bibr">27</xref>]. However, the surface hydrophobicity, as well as the charge density, strongly influences the elimination rate [<xref rid="B28-cancers-11-01855" ref-type="bibr">28</xref>].</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">SHAPE</td><td align="left" valign="middle" rowspan="1" colspan="1">NCs’ shape determines the movement in blood circulation and the organ-specific biodistribution [<xref rid="B25-cancers-11-01855" ref-type="bibr">25</xref>]. Spherical NCs presented the longest circulation time, while rod-, disc-, cage- particles exhibited an increased splenic and hepatic accumulation compared with spherical counterparts [<xref rid="B29-cancers-11-01855" ref-type="bibr">29</xref>].</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">STIFFNESS</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Due to the intrinsic deformability, soft NCs have prolonged circulation lifetimes and reduced splenic accumulation when compared with rigid NCs [<xref rid="B30-cancers-11-01855" ref-type="bibr">30</xref>].</td></tr></tbody></table></table-wrap><table-wrap id="cancers-11-01855-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">cancers-11-01855-t002_Table 2</object-id><label>Table 2</label><caption><p>Clinically approved cancer nanomedicines [<xref rid="B8-cancers-11-01855" ref-type="bibr">8</xref>,<xref rid="B31-cancers-11-01855" ref-type="bibr">31</xref>].</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Product Name</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Composition</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Indications</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">First Approval</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">Doxil/Caelyx</td><td align="center" valign="middle" rowspan="1" colspan="1">PEGylated liposomal doxorubicin</td><td align="center" valign="middle" rowspan="1" colspan="1">Myeloma, Kaposi’s sarcoma, breast, and ovarian cancer</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in the US (1995)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">DaunoXome</td><td align="center" valign="middle" rowspan="1" colspan="1">liposomal daunorubicin</td><td align="center" valign="middle" rowspan="1" colspan="1">Kaposi’s sarcoma</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in the US (1996)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Myocet</td><td align="center" valign="middle" rowspan="1" colspan="1">liposomal doxorubicin</td><td align="center" valign="middle" rowspan="1" colspan="1">Breast cancer</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in Europe/Canada (2000)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Abraxane</td><td align="center" valign="middle" rowspan="1" colspan="1">albumin-bound paclitaxel</td><td align="center" valign="middle" rowspan="1" colspan="1">Breast, non-small-cell lung, and pancreatic cancer</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in the US (2005)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Lipusu</td><td align="center" valign="middle" rowspan="1" colspan="1">liposomal paclitaxel</td><td align="center" valign="middle" rowspan="1" colspan="1">Breast and non-small-cell lung cancer</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in China (2006)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Oncaspar</td><td align="center" valign="middle" rowspan="1" colspan="1">L-asparaginase conjugate</td><td align="center" valign="middle" rowspan="1" colspan="1">Acute lymphoblastic leukemia</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in the US (2006)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">DepoCyt</td><td align="center" valign="middle" rowspan="1" colspan="1">liposomal cytarabine</td><td align="center" valign="middle" rowspan="1" colspan="1">Lymphoma, Leukemia</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in the US (1999)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Genexol-PM</td><td align="center" valign="middle" rowspan="1" colspan="1">paclitaxel micellar</td><td align="center" valign="middle" rowspan="1" colspan="1">Breast, non-small-cell lung, ovarian, and gastric cancer</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in Korea (2007)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Mepact</td><td align="center" valign="middle" rowspan="1" colspan="1">liposomal mifamurtide</td><td align="center" valign="middle" rowspan="1" colspan="1">Osteogenic sarcoma</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in Europe (2009)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">NanoTherm</td><td align="center" valign="middle" rowspan="1" colspan="1">Iron oxide nanoparticles</td><td align="center" valign="middle" rowspan="1" colspan="1">Brain tumors</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in Europe (2011)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Marqibo</td><td align="center" valign="middle" rowspan="1" colspan="1">Liposomal vincristine sulfate</td><td align="center" valign="middle" rowspan="1" colspan="1">Acute lymphoblastic leukemia</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in the US (2012)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">ONIVYDE</td><td align="center" valign="middle" rowspan="1" colspan="1">liposomal irinotecan</td><td align="center" valign="middle" rowspan="1" colspan="1">Advanced pancreatic cancer</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in the US (2015)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">DHP107</td><td align="center" valign="middle" rowspan="1" colspan="1">paclitaxel lipid nanoparticles (oral administration)</td><td align="center" valign="middle" rowspan="1" colspan="1">Gastric cancer</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in Korea (2016)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Vyxeos</td><td align="center" valign="middle" rowspan="1" colspan="1">liposomal daunorubicin and cytarabine</td><td align="center" valign="middle" rowspan="1" colspan="1">High-risk acute myeloid leukemia</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in the US (2017)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Apealea</td><td align="center" valign="middle" rowspan="1" colspan="1">paclitaxel micellar</td><td align="center" valign="middle" rowspan="1" colspan="1">Ovarian, peritoneal, and fallopian tube cancer</td><td align="center" valign="middle" rowspan="1" colspan="1">Approved in Europe (2018)</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hensify</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">hafnium oxide nanoparticles</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Locally-advanced soft tissue sarcoma</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Approved in Europe (2019)</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>Italie</li></country></list><tree><noCountry><name sortKey="Bertolini, Jessica Armida" sort="Bertolini, Jessica Armida" uniqKey="Bertolini J" first="Jessica Armida" last="Bertolini">Jessica Armida Bertolini</name><name sortKey="Colombo, Miriam" sort="Colombo, Miriam" uniqKey="Colombo M" first="Miriam" last="Colombo">Miriam Colombo</name><name sortKey="Pandolfi, Laura" sort="Pandolfi, Laura" uniqKey="Pandolfi L" first="Laura" last="Pandolfi">Laura Pandolfi</name><name sortKey="Rizzuto, Maria Antonietta" sort="Rizzuto, Maria Antonietta" uniqKey="Rizzuto M" first="Maria Antonietta" last="Rizzuto">Maria Antonietta Rizzuto</name><name sortKey="Salvioni, Lucia" sort="Salvioni, Lucia" uniqKey="Salvioni L" first="Lucia" last="Salvioni">Lucia Salvioni</name></noCountry><country name="Italie"><noRegion><name sortKey="Prosperi, Davide" sort="Prosperi, Davide" uniqKey="Prosperi D" first="Davide" last="Prosperi">Davide Prosperi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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