Abstract
The recent novel approach of third level drug targeting directly within the intracellular locations can enhance the efficiency of treatment procedures to new heights. Cells usually consume the drugs and drug carriers by receptor mediated endocytosis which ultimately results in their lysosomal degradation, leaving behind a very small amount (similar to 0.1%) for organelle specific point of action. Previously these obstacles were being solved inappropriately by using large quantities of native drugs as single or multiple doses. This complication has been bypassed by many innovative strategies, especially for the cancer treatment. The discovery of different organelle specific targeting ligands (folic acid, cell penetrating proteins, nuclear localization signal, triphenyl-phosphonium, mannose-6-phosphate, etc.) and its conjugation with drugs or drug carriers have revolutionized the therapeutics to specific point of treatment. Different anticancer drugs (doxorubicin, cisplatin, paclitaxel, etc.) loaded in varied types of nanoparticles (NPs) (polymers, micelles, liposomes etc.) have been directly targeted to different organelles. This approach has also been used for gene therapy for mitochondrial and nuclear genome originated diseases. Different diseases like Alzheimer's disease, lysosomal storage diseases, cancer, etc. have shown quite positive results with the help of organelle-specific drug targeting approach. Several drug carrying NPs like Abraxane, Doxil etc. have been clinically approved besides several other drug-nanocarrier formulations, which are still in clinical trials. This review highlights current strategies for intracellular drug targeting which includes the use of small molecules, peptides, and pH sensitive liposomes and other nanoformulations. The intracellular target includes nuclei for gene therapy, mitochondria for pro-apoptotic cancer therapy and lysosomes for enzyme therapy for lysosomal storage diseases. The organelle-specific drug targeting faces many challenges but has a great future ahead for therapeutics.