PMID- 33261651 OWN - NLM STAT- MEDLINE DCOM- 20210928 LR - 20210928 IS - 1477-3155 (Electronic) IS - 1477-3155 (Linking) VI - 18 IP - 1 DP - 2020 Dec 1 TI - Functionalized silk spheres selectively and effectively deliver a cytotoxic drug to targeted cancer cells in vivo. PG - 177 LID - 10.1186/s12951-020-00734-y [doi] LID - 177 AB - BACKGROUND: Chemotherapy is often a first-line therapeutic approach for the treatment of a wide variety of cancers. Targeted drug delivery systems (DDSs) can potentially resolve the problem of chemotherapeutic drug off-targeting effects. Herein, we examined in vivo models to determine the efficacy of Her2-targeting silk spheres (H2.1MS1) as DDSs for delivering doxorubicin (Dox) to Her2-positive and Her2-negative primary and metastatic mouse breast cancers. RESULTS: The specific accumulation of H2.1MS1 spheres was demonstrated at the site of Her2-positive cancer. Dox delivered only by functionalized H2.1MS1 particles selectively inhibited Her2-positive cancer growth in primary and metastatic models. Moreover, the significant effect of the Dox dose and the frequency of treatment administration on the therapeutic efficacy was indicated. Although the control MS1 spheres accumulated in the lungs in Her2-positive metastatic breast cancer, the Dox-loaded MS1 particles did not treat cancer. Histopathological examination revealed no systemic toxicity after multiple administrations and at increased doses of Dox-loaded silk spheres. Although the studies were performed in immunocompetent mice, the H2.1MS1 silk spheres efficiently delivered the drug, which exerted a therapeutic effect. CONCLUSION: Our results indicated that functionalized silk spheres that enable cell-specific recognition, cellular internalization, and drug release represent an efficient strategy for cancer treatment in vivo. FAU - Florczak, Anna AU - Florczak A AD - Chair of Medical Biotechnology, Poznan University of Medical Sciences, 15 Garbary St, 61-866, Poznan, Poland. annaflorczak@ump.edu.pl. AD - Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61-866, Poznan, Poland. annaflorczak@ump.edu.pl. FAU - Deptuch, Tomasz AU - Deptuch T AD - Chair of Medical Biotechnology, Poznan University of Medical Sciences, 15 Garbary St, 61-866, Poznan, Poland. AD - Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61-866, Poznan, Poland. FAU - Lewandowska, Anna AU - Lewandowska A AD - Department of Tumor Pathology, Greater Poland Cancer Centre, 15 Garbary St, 61-866, Poznan, Poland. AD - Department of Tumor Pathology and Prophylaxis, Poznan University of Medical Sciences, 15 Garbary St, 61-866, Poznan, Poland. FAU - Penderecka, Karolina AU - Penderecka K AD - Chair of Medical Biotechnology, Poznan University of Medical Sciences, 15 Garbary St, 61-866, Poznan, Poland. AD - Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61-866, Poznan, Poland. FAU - Kramer, Elzbieta AU - Kramer E AD - Department of Tumor Pathology, Greater Poland Cancer Centre, 15 Garbary St, 61-866, Poznan, Poland. FAU - Marszalek, Andrzej AU - Marszalek A AD - Department of Tumor Pathology, Greater Poland Cancer Centre, 15 Garbary St, 61-866, Poznan, Poland. AD - Department of Tumor Pathology and Prophylaxis, Poznan University of Medical Sciences, 15 Garbary St, 61-866, Poznan, Poland. FAU - Mackiewicz, Andrzej AU - Mackiewicz A AD - Chair of Medical Biotechnology, Poznan University of Medical Sciences, 15 Garbary St, 61-866, Poznan, Poland. AD - Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61-866, Poznan, Poland. FAU - Dams-Kozlowska, Hanna AU - Dams-Kozlowska H AUID- ORCID: 0000-0003-2349-419X AD - Chair of Medical Biotechnology, Poznan University of Medical Sciences, 15 Garbary St, 61-866, Poznan, Poland. hanna.dams-kozlowska@wco.pl. AD - Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61-866, Poznan, Poland. hanna.dams-kozlowska@wco.pl. LA - eng GR - 2014/15/B/NZ7/00903/Narodowe Centrum Nauki/ PT - Journal Article DEP - 20201201 PL - England TA - J Nanobiotechnology JT - Journal of nanobiotechnology JID - 101152208 RN - 0 (Antineoplastic Agents) RN - 0 (Silk) RN - 80168379AG (Doxorubicin) SB - IM MH - Animals MH - *Antineoplastic Agents/chemistry/pharmacokinetics/pharmacology MH - Cell Line, Tumor MH - *Doxorubicin/chemistry/pharmacokinetics/pharmacology MH - Drug Delivery Systems/*methods MH - Female MH - Humans MH - Mammary Neoplasms, Experimental/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Nanoparticles/*chemistry MH - *Silk/chemistry/pharmacokinetics PMC - PMC7709326 OTO - NOTNLM OT - Bioengineering OT - Cancer OT - Functionalization OT - Mouse cancer models OT - Particles OT - Silk OT - Targeted drug delivery COIS- The authors declare that they have no competing interests. EDAT- 2020/12/03 06:00 MHDA- 2021/09/29 06:00 PMCR- 2020/12/01 CRDT- 2020/12/02 05:21 PHST- 2020/09/25 00:00 [received] PHST- 2020/11/19 00:00 [accepted] PHST- 2020/12/02 05:21 [entrez] PHST- 2020/12/03 06:00 [pubmed] PHST- 2021/09/29 06:00 [medline] PHST- 2020/12/01 00:00 [pmc-release] AID - 10.1186/s12951-020-00734-y [pii] AID - 734 [pii] AID - 10.1186/s12951-020-00734-y [doi] PST - epublish SO - J Nanobiotechnology. 2020 Dec 1;18(1):177. doi: 10.1186/s12951-020-00734-y.