Abstract
Cancer is one of the major causes of death worldwide and its treatment remains very challenging. The effectiveness of cancer therapy significantly depends upon tumour-specific delivery of the drug. Nanoparticle drug delivery systems have been developed to avoid the side effects of the conventional chemotherapy. However, according to the most recent recommendations, future nanomedicine should be focused mainly on active targeting of nanocarriers based on ligand-receptor recognition, which may show better efficacy than passive targeting in human cancer therapy. Nevertheless, the efficacy of single-ligand nanomedicines is still limited due to the complexity of the tumour microenvironment. Thus, the NPs are improved toward an additional functionality, e.g., pH-sensitivity (advanced single-targeted NPs). Moreover, dual-targeted nanoparticles which contain two different types of targeting agents on the same drug delivery system are developed. The advanced single-targeted NPs and dual-targeted nanocarriers present superior properties related to cell selectivity, cellular uptake and cytotoxicity toward cancer cells than conventional drug, non-targeted systems and single-targeted systems without additional functionality. Folic acid and biotin are used as targeting ligands for cancer chemotherapy, since they are available, inexpensive, nontoxic, nonimmunogenic and easy to modify. These ligands are used in both, single- and dual-targeted systems although the latter are still a novel approach. This review presents the recent achievements in the development of single- or dual-targeted nanoparticles for anticancer drug delivery.
Highlights
According to the World Cancer Report [1], cancer is the first or second leading cause of premature death in 134 of 183 countries and it ranks third or fourth in an additional 45 countries
The era of biotinylated drug delivery systems (DDSs) has been started from the article published in 2004 by Russell-Jones et al It has been reported that the therapy of colon cancer with the biotin-labelled doxorubicinhydroxypropylmethacrylic acid (Dox-HMPA) complex provides enhanced efficiency when compared to the control group
There is a concept of using combination of folic acid and biotin as targeting ligands [173]: one of the first papers dealing with the evaluation of the effectiveness of folate, vitamin B12 or biotin-functionalized polymeric materials as active drug targeting agents to tumour cells was published in 2004 by Russell-Jones et al It has been reported that the cells overexpressing the receptors for folate or vitamin B12, overexpress receptors for biotin [119]
Summary
According to the World Cancer Report [1], cancer is the first or second leading cause of premature death (i.e., at ages 30–69 years) in 134 of 183 countries and it ranks third or fourth in an additional 45 countries. Apart from surface modification for achieving the active targeting, the liposomes may respond to the specific properties of the cancer cell environment to release anti-cancer drugs under well-defined conditions, e.g., pH, ultrasounds, magnetic field exposure, light, enzymes, thereby reducing systemic toxicity to healthy cells [9]. The magnetoliposomes may be excited by magnetic radiation that cause local hyperthermia within the tumor leading to the cancer cell death Such transport systems, in addition, to their chemotherapeutic properties, can be used in cancer diagnostics (e.g., with the use of MRI) and may be promising in the future cancer therapy [10,11]. It has been demonstrated that substantial intra- and intertumoural variability is present in the tumour cells and the tumour microenvironment that results in the heterogeneity of molecular, pathologic and clinical features of each tumour type In this aspect, the nanoparticle design plays a significant role in influencing tumour targeting [5].
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