Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies

Abstract

Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy.

Monocorevs.multicore magnetic iron oxide nanoparticles: uptake by glioblastoma cells and efficiency for magnetic hyperthermia

“…The higher efficiency of the multicore IONPs compared to the monocore IONPs was evidenced by an increased cytotoxicity that appeared also to be independent of the iron oxide dose. Therefore multicore IONPs or nanoflowers are particularly suitable agents for magnetic hyperthermia treatment of cancerous cells, and a lot of research is currently on-going in our group and others to design molecular coatings providing further functionalities such as cancer cell targeting, 43 or anticancer drug delivery activated by the AMF application.…”

Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

“…Because of the side effect profiles of generic cancer chemotherapeutic agents, there is substantial interest in developing molecular mechanisms that direct these drugs specifically to cancer cells. [6][7][8][9][10][11] Tetraiodothyroacetic acid (tetrac) is a ligand of a specific target on the extracellular domain of plasma membrane integrin αvβ3, 12 an integrin generously expressed by cancer cells and by dividing endothelial cells of tumor-relevant blood vessels. We have covalently bonded tetrac via a short diaminopropane linker to a 150-200 nm poly(lactic-co-glycolic acid) (PLGA) nanoparticle (Nanotetrac, nano-diamino-tetrac [NDAT]), as shown in Figure 1.…”

Magnetic Nanocarriers Enhance Drug Delivery Selectively to Human Leukemic Cells

“…The main advantages of using MNPs for such purposes are: 1) easy preparation; 2) small sizes and large surface areas; 3) facile chemical functionalization; 3) excellent biocompatibility and stability; 4) efficient drug conjugation; and 5) superior magnetic responsiveness. Such unique properties of MNPs enabled their use as MRI contrast agents, hyperthermia agents, magnetic field guided localization vectors, and/or drug delivery vehicles [17]. Hence, MNPs are excellent candidates for targeted drug delivery and image-guided therapeutics with a great potential in clinical cancer theranostics [18,19].…”