The key to the success of siRNA therapy depends on the use of siRNA delivery agents that effectively penetrate tumor cells and simultaneously protect siRNA from RNase attacks. Sucrose esters (SEs) are found to have tremendous potential applications in siRNA delivery because of their biocompatibility and low toxicity. However, the esterification of sucrose yields complex mixtures that greatly limit their progress in this field. We synthesized a series of novel sucrose monoester-based cationic lipids (SECLs) by using 1 & PRIME;,4,6 & PRIME;trichlorogalactosucrose (TGS) to achieve monoesterification of sucrose. SECL-based liposomes formed from these lipids and colipids [dioleoylphosphatidylethanolamine (DOPE) or cholesterol (Chol)] could effectively condense genes into nanocomplexes, which exhibited significantly higher uptake rates and gene silencing efficiency than 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) liposome. Furthermore, SECL-based liposomes containing cholesterol-mediated IGF-1R siRNA delivery could inhibit tumor growth by the downregulation of Bcl-2 and the upregulation of Bax. Most importantly, these liposomes displayed low cytotoxicity in vitro and in vivo because they could be degraded under tumor acidic pH environments. Our study establishes a novel method for the synthesis of SEs from TGS and demonstrates the applicability of SECLs for gene delivery with the potential for clinical therapy. [GRAPHICS]

The success of skin cancer treatment is severely limited in the route of administration because most genes and drugs cannot break through the excellent stratum corneum (SC) barrier of the skin, leading to their inability to reach the tumor tissues at therapeutic doses. As an excellent minimally invasive delivery method, microneedles (MNs) can bypass the SC and enter the skin microcirculation to achieve drug and gene delivery when used to puncture the skin. Compared with traditional administration approaches, MN-assisted gene and drug delivery have obvious advantages, in that they are simple, safe, painless, easily transport genes (such as DNA and siRNA (small interfering RNA)) and macromolecule drugs (including proteins and antibodies), and have good reproducibility. Besides, other treatment strategies including photothermal therapy (PTT) have been combined with MN arrays containing genes or drugs, which is expected to improve the therapeutic effect of skin cancer. Therefore, this review summarizes the latest developments in MNs for gene and/or drug delivery, with a focus on their performances as effective MNs for skin cancer treatment.

Conventional chemotherapy for tumor treatment remains flawed because it fails to limit cytotoxicity to a small set of selectable tissues. Active targeting techniques for the delivery of drugs to specific sites are increasingly used to enhance drug accumulation at tumor sites with the aim of reducing side effects in vivo. Liposomes, modified with different targeting ligands, are considered to be one of the most promising targeted drug carriers. Herein, novel linear and cyclic arginine-glycine-aspartate (RGD) peptide-based lipids were synthesized to develop modified liposomal drug delivery systems with active targeting and pH-sensitivity. The RGD-modified liposomes showed excellent active targeting ability for integrin αvβ3 receptors, resulting in improved cellular uptake. The modified liposomes also enhanced intracellular doxorubicin (DOX) release because of their degradation in an acidic environment. Consequently, the RGD-modified, DOX-loaded liposomes exhibited significant antitumor efficacy and low toxicity in vitro and in vivo. In particular, 5% cRGD-lipid modified DOX-loaded liposome showed the greatest inhibition of tumor growth in mice among the tested formulations, and much less toxicity than free DOX. In conclusion, the DOX-loaded pH-sensitive liposome modified with 5% cRGD-lipid developed in the current study provides a potential approach for improved tumor therapy.

Microneedles (MNs), as an effective minimally invasive delivery route, when used to puncture the skin, can bypass the skin's stratum corneum (SC) to enter the skin microcirculation and achieve systemic administration. Additionally, the MN route has obvious advantages over other routes of administration, including simplicity, non-pain, readily-permitted transport of drugs (including DNA and metformin) and macromolecules (such as antibodies and proteins), good repeatability, and wide range of clinical applications and safety. MNs have been combined with various therapy strategies including photodynamic therapy (PDT) and photothermal therapy (PTT) to treat many diseases, and hold great promise for improving the diagnosis and treatment of diseases. Both MN-assisted PDT and PTT are light-mediated phototherapy methods and have unique advantages, including improved selectivity, and minimal invasiveness and side effects. MN-assisted PDT or PTT has been studied for various applications by many research groups and pharmaceutical companies worldwide. Therefore, this review summarizes recent advances in MNs for PDT or PTT.

Among various nanoparticles, superparamagnetic iron oxide nanoparticles (SPIONs) have been increasingly studied for their excellent superparamagnetism, magnetic heating properties, and enhanced magnetic resonance imaging (MRI). The conjugation of SPIONs with drugs to obtain delivery nanosystems has several advantages including magnetic targeted functionalization, in vivo imaging, magnetic thermotherapy, and combined delivery of anticancer agents. To further increase the targeting efficiency of drugs through a delivery nanosystem based on SPIONs, additional targeting moieties including transferrin, antibodies, aptamers, hyaluronic acid, folate, and targeting peptides are coated onto the surface of SPIONs. Therefore, this review summarizes the latest progresses in the conjugation of targeting molecules and drug delivery nanosystems based on SPIONs, especially focusing on their performances to develop efficient targeted drug delivery systems for tumor therapy.