Table 2.

Drug delivery systems for anti-tumor drugs.

Nanocarrier Type [Size Range]	Significant Properties	Selected Studies
Organic nanocarriers
Solid lipid nanoparticles (SLNs) [50–200 nm]	Economical large-scale production, high drug payload, better stability and easy to handle, improved bioavailability of poorly water-soluble drugs, as well as lack of biotoxicity.	In 2017, Wang et al. have designed resveratrol-loaded SLNs (Res-SLNs) to treat breast cancer cells. They showed that Res-SLNs significantly exhibited the inhibitory effects on cancer cells proliferation, invasion and migration, compared to controls [46].
Liposomes and polymersomes [30 nm–110 nm]	Enhanced delivery of drugs, preventing early degradation of the encapsulated drug, cost-effective formulations of expensive drugs and efficient treatment, improved performance features of the product, protection of the active drug from environmental factors, as well as reduced systemic toxicity. Weak mechanical properties of liposomes may be enhanced by using polymeric liposomes called polymersomes [47]. Possibility to encapsulate hydrophobic drugs in the lipidic bilayer, as well as hydrophilic drugs in the hydrophilic core [48].	Doxorubicin (DOX)-loaded specific monoclonal antibodies conjugated to liposomes were used to treat lung tumor in mice. The results showed significant suppression of tumor growth, metastatic spread and increased the survival rate of the tumor-bearing mice compared to controls [49].
Dendrimers [1.5–14.5 nm]	The most utilized nanocarrier owing to their incomparable characteristics, including the increased number of branching, distinctive molecular weight, monodispersed macromolecules, multivalency and spherical shapes.	In treating of lung metastasis mouse model, as indicated by increased survival rates and decreased tumor burden, DOX conjugated to carboxyl-terminated poly(amidoamine) dendrimers (PAMAM) was more effective than DOX delivered intravenously [50].
Polymeric nanoparticles (PNPs) [10–200 nm]	Two types: -Nanospheres PNPs (matrix-type); disperse the drug in the polymer matrix. -Nanocapsules PNPs (reservoir-type); dissolve the drug in aqueous or oily liquid covered by a solid polymeric membrane. PNPs are highly versatile based on a wide range of polymers from synthetic and natural sources. The modification of the physicochemical properties of the polymers used to produce PNPs can accurately control the degradation of PNPs and drug release.	Nanoscale coordination polymer-1 (NCP-1) has been used for simultaneous delivery of Oxaliplatin and Gemcitabine monophosphate. NCP-1 particles effectively avoided uptake by the mononuclear phagocyte system (MPS), which is resulted in potently delivery for both drugs and thus a strong synergistic therapeutic effect was observed against pancreatic cancer cells by inhibiting tumor growth [51].
Polymeric micelles (PMs) [10–100 nm]	PMs allow hydrophobic drugs to be entrapped into their cores which enhance their water solubility. The hydrophilic shell of PMs promotes their stability and their circulation times in blood by preventing the recognition and subsequent uptake of it by the reticule endothelial system.	Pluronic micelles combined with polyplexes spontaneously were used as amphiphilic-based gene delivery system with two breast cancer cell lines. This system has been formed by electrostatic interaction between cationic polyethyleneimine and anionic siRNA against AKT2. After treatment, a significant reduction was observed on cell invasion capacity, as well as a significant inhibition of mammosphere formation [52].
Virus-based nanoparticles (VNPs) [up to 100 nm]	VNPs emerged based on their easy surface functionalization, availability in a variety of sizes and shapes, in addition to their biocompatibility and morphological uniformity.	To overcome immunological tolerance against human epidermal growth factor receptor 2 (HER2) in breast cancer mouse model, HER2 epitopes were integrated on the plant-produced vaccination platform potato virus X (PVX). The results showed that this carrier stimulated the production of HER2-specific antibodies in the injected mice [53].
Inorganic nanocarriers
Carbon nanotubes (CNTs) [0.4–100 nm]	Able to cross the cell membrane via endocytosis and subsequently enter into the cell; based on their needle-like shape. With its physicochemical characteristics, CNTs able to carry high drug amounts, structural flexibility and intrinsic stability and appropriate surface functionalization.	In 2010, Sun et al. have conjugated MCF7 breast cancer cells−derived tumor lysate (covalent) to Carboxylated MWNT (CNTs) in vitro. They reported increased antigen uptake by dendritic cells (DCs) and improved the induction of tumor−specific T cell response by DCs, thus enhance the uptake of tumor antigens [54].
Mesoporous silica nanoparticles (MSNs) [2–50 nm]	Owing to their honeycomb-like shape with hundreds of pores, MSNs able to load large drugs amounts. Based on their ease of surface functionalization for targeted and controlled drug delivery, MSNs reduce the toxicity of drugs and promote therapeutic efficacy.	Guo et al. have used MSNs with nuclear targeting in cancer therapy for multidrug resistance (MDR) breast cancer cells. They used a size changeable MSNs able to alter to smaller micelles under specific conditions. This study reported this type of MSNs as a highly effective delivery system for anticancer drugs to the nucleus of MDR cancer cells, directly [55].
Hybrid nanocarriers	A combination of organic and inorganic NPs. This combination successfully employed specific functionalities of both NPs to enhance the selectivity and efficiency of drugs along with high payload sustained and intracellular delivery.	A multifunctional hybrid nanocarrier was developed by merging the properties of pH-sensitive nanogels and multiwall carbon nanotube, to deliver the DOX. This study showed a significant effect of DOX supernatant with this hybrid nanocarrier on the U-87 glioblastoma cancer cells proliferation suppression [56].