Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations.
We report the development of a chemotherapeutic nanoformulation made of polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as a promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake and cell death were evaluated in three types of human breast cells: two metastatic cancerous MCF-7 and MDA-MB-231 cells and nontumorigenic MCF-10A cells. While Fl-PMNPs were not toxic to cells even at the highest concentrations used, Dox-loaded Fl-PMNPs showed significant potency, effectively killing the different breast cancer cells, albeit at different affinities. Interestingly and superior to free Dox, Dox-loaded Fl-PMNPs were found to be more effective in killing the metastatic cells (2- to 3-fold enhanced cytotoxicities for MDA-MB-231 compared to MCF-7), compared to the normal noncancerous MCF-10A cells (up to 8-fold), suggesting huge potentials as selective anticancer agents. Electron and live confocal microscopy imaging mechanistically confirmed that the nanoparticles were successfully endocytosed and packaged into vesicles inside the cytoplasm, where Dox is released and then translocated to the nucleus exerting its cytotoxic action and causing apoptotic cell death. Furthermore, commendable and enhanced penetration in 3D multilayered primary tumor cells derived from primary lesions as well as in patient breast tumor biopsies was observed, killing the tumor cells inside. The designed nanocarriers described here can potentially open new opportunities for breast cancer patients, especially in theranostic imaging and hyperthermia. While many prior studies have focused on targeting ligands to specific receptors to improve efficacies, we discovered that even with passive-targeted tailored delivery system enhanced toxic responses can be attained.
King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, National Guard Health Affairs, Riyadh 11481, Saudi Arabia.|King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Hospital, Riyadh 11426, Saudi Arabia.
Kheireddine
K
El-Boubbou
King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Hospital, Riyadh 11426, Saudi Arabia.
Rizwan
R
Ali
King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Hospital, Riyadh 11426, Saudi Arabia.
Hassan M
HM
Bahhari
King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Hospital, Riyadh 11426, Saudi Arabia.
Khaled O
KO
AlSaad
King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Hospital, Riyadh 11426, Saudi Arabia.
Atef
A
Nehdi
King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Hospital, Riyadh 11426, Saudi Arabia.
Mohamed
M
Boudjelal
King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, National Guard Health Affairs, Riyadh 11481, Saudi Arabia.
Abdulmohsen
A
AlKushi
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001692:Biological Transport; D001706:Biopsy; D001943:Breast Neoplasms / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004339:Drug Compounding; D005290:Ferric Compounds / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005290:Ferric Compounds; D005456:Fluorescent Dyes; C000499:ferric oxide; D004317:Doxorubicin; D011205:Povidone