Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

Abstract

Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic-organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the "state of the art" of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.

Keywords: cell targeting; drug delivery; multifunctional nanocarriers; stimuli responsive; surface modification; toxicity.

Figure 1

Representative nanoparticles that are used as appropriate drug delivery vehicles and their interactions with stem cells [13].

Figure 2

(a) Surface modification of carbon nanotubes (CNTs) with biocompatible PEGylated polymers [46]; (b) Schematic illustration of folate-targeted and fluorescently labeled multifunctional multiwalled carbon nanotubes (MWCNTs) for targeted and pH-responsive delivery of doxorubicin (DOX) to cancer cells [48].

Figure 3

Synthetic path of DOX loaded HA-Q-G-RBITC multifunctional nanosheets and HA-Mediated Endocytosis [78].

Figure 4

Synthesis of polymer functionalized gold nanoparticles and their conjugation to the anticancer drug Au(1)PPh3 [104].

Figure 5

(A) Functionalization procedure of MSNs; (B) Drug-loaded MSNs under physiological condition; (C) RGDS-targeted to the tumour cell; (D) Endocytosis into specific tumour cell; (E) CathepsinB enzyme-triggered drug release in cytoplasm; (F) Apoptosis of the tumour cell [146].

Figure 6

Structures of (a) solid lipid based nanocarriers (b) nanostructured lipid carriers.

Figure 7

Schematic presentation of functionalized liposomes (pink sphere) with breast cancer targeting peptide (purple structure) and confocal images of liposomes (green spheres) in fluorescein isothiocyanate [217].

Figure 8

Multifunctional lactobionic acid-modified dendrimers for targeted drug delivery to liver cancer cells [223].

Figure 9

CS nanocarriers for several medical and pharmaceutical applications.

Figure 10

Multifunctional poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) nanoparticles for cancer cell targeting and imaging [288].

Figure 11

Synthesis of folate-pegylated polyester nanoparticles encapsulating ixabepilone (red spheres) for targeting folate receptor overexpressing breast cancer cells (blue cells) [2].