Tumor remission in Yoshida sarcoma-bearing rts by selective targeting of magnetic albumin microspheres containing doxorubicin.

Abstract

Magnetically responsive albumin microspheres containing doxorubicin and magnetite (Fe3O,) were selectively targeted to Yoshida sarcoma tumors in rats by utilizing an extracorporeal magnet. Tumor cells were inoculated subcutaneously in the tail ofrats, and the tumors were allowed to grow to an average size of 9 X 45 mm prior to initiating treatment. Drug-bearing microspheres (0.5 mg ofdoxorubicin per kg ofbody weight) were infused proximal to the tumor through the ventral caudal artery while the tumor was exposed to an external magnetic field of 5500 Oe for 30 min. Control animals received free doxorubicin administered either intravenously (5 mg/kg) or infused intraarterially (5 and 0.5 mg/kg), drug-bearing microspheres infused intraarterially (0.5 mg/kg) without the external magnet, or placebo microspheres with magetic localization. Ofthe 12 animals treated with a single dose in the experimental group, 9 exhibited total remission of the tumor, representing a disappearance of tumors as large as 60 mm in length. Marked tumor regression was observed in the remaining three rats, and no deaths or metastases occurred in the experimental group. In contrast, significant increases in tumor size with widespread metastases occurred in all control groups and most rats died. These experiments indicate that targeting of oncolytic agents to solid neoplasms by magnetic microspheres may be a means of increasing the efficacy and decreasing the toxicity of antitumor agents.The ability to selectively target and restrict activity of antineoplastic agents to known foci of tumors has been a continuous challenge in cancer chemotherapy. Encapsulation carriers such as liposomes (1, 2) and albumin microspheres (3, 4) offer promise for attaining target-site specificity. However, the unrestricted circulation of liposomes and other carriers results in their rapid clearance by the, reticuloendothelial system if injected intravascularly. Moreover, neither modality has demonstrated a significant degree oftarget-site specificity. The various modalities for the targeting of drugs have recently been extensively reviewed (5) and will not be discussed here.With the goal of circumventing the reticuloendothelial system and achieving high target-area concentrations of drug carrier, we designed small (1-,m average diameter) magnetically responsive albumin microspheres capable of responding to extracorporeal magnetic fields (6). Virtually any water-soluble drug can be entrapped in these microspheres. By varying magnetic parameters, we have shown in vitro that the microspheres could be selectively retained at capillary-level flow rates (7). Retention ofthe drug carrier in capillaries is important, as maximum drug diffusion occurs at this level ofthe circulation. In addition, one ideally would like to remove the carrier from the vascular system into the extravascular compartment, producing a depot for sustained release ofantineoplastic agents. We have demonstrated that as early as 30 min after drug-carrier lo-

Nucleic Acid Delivery and Localizing Delivery with Magnetic Nanoparticles

“…The treatment was therapeutically effective in that it resulted in total tumor remission in a high percentage of experimental animals. In contrast, animals treated with free doxorubicin, placebo microspheres, or nonlocalized doxorubicin microspheres exhibited a significant increase in tumor size with metastases and subsequent death in 90-100% of the animals [179,180]. Other researchers obtained similar results [181][182][183][184][185][186][187].…”

Co-encapsulation of magnetic Fe3O4 nanoparticles and doxorubicin into biodegradable PLGA nanocarriers for intratumoral drug delivery

“…MNPs have been widely used in the delivery of chemotherapeutics, achieving promising results. [19][20][21][22][23] The authors propose that combining intratumoral administration with a magnetic nanocarrier in chemotherapy provides opportunities for treating cancers in a safe and effective manner. In this study, the authors fabricated a MNP drug delivery system for intratumoral administration that was comprised of magnetic efficiency, and they supported a sustained and steady release of DOX.…”

Photosensitized destruction of human bladder carcinoma cells treated with chlorin e6-conjugated microspheres.

“…have found many biologic applications (18), including enhanced delivery of drugs and toxins (19), cell sorting by density-gradient (20) and magnetic (21) techniques, measurement of blood flow (22), and probing of neuroanatomic pathways and neurophysiology (23). The present study describes Phototoxicity Assay.…”