Table 1.

The advantages and disadvantages of main drug delivery approaches. Abbreviations: ADC, antibody-drug conjugated; EVs, extracellular vesicles.

Strategy	Advantages	Disadvantages	References
Nanoparticles	• Flexibility • High stability in vivo • Increased compound half-life • Hydrophilic and lipophilic compounds can be both loaded • Enhanced permeability of tumor vasculature facilitates nanoparticle delivery on the tumor site	• Depends on the nanoparticle type • Inorganic nanoparticles may trigger the immune-system	[19,20,21,22,23,24,25,26,27,28]
Liposomes	• Similarity with cell membrane • High variety of drug encapsulation • Low systemic toxicity	• Sensitivity to sterilization methods • Low stability in circulation • Low reproducibility in liposome loading and size control • Short shelf-life	[29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]
Polymer Conjugated Drugs	• Increased compound half-life • Increased high-dose drug tolerance • Increased specificity	• Deep knowledge of polymer–receptor molecular interactions required • Poor information about long-term side effects	[44,45,46,47,48,49,50,51,52,53,54]
Small molecules, peptides and antibodies	• Various anticancer effects • High cell permeability • Low systemic toxicity	• Depends on the small molecule type • Size-influenced pharmacokinetics • Short half-life	[55,56,57,58,59,60,61,62,63,64,65,66,67,68,69]
ADC	• High specificity • Remarkable results for AB working as single entities	• May trigger the immune system • High production costs • Some clinical trials showed no significant improvement of patient outcomes compared to canonical therapies	[4,70,71,72,73,74,75,76,77,78]
Reconfigurable Organisms	• Extremely configurable organisms • High drug loading efficiency • Autonomous, self-repairing system	• Machine learning is still unripe • Research in this field is still in the embryonic stage	[79]
EVs	• High biocompatibility due to the endogenous origin • High specificity • Can be highly modified in order to enhance or modify tissue specificity • Due to the phospholipid bilayer, they can easily fuse directly to the target’s plasma membrane • Presence of specific surface markers that preserve them from phagocytosis • Functional complexity, not easy to artificially replicate	• Generally low efficiency of EVs isolation methods • Lack of clinical evaluations • Lack of standardized isolation methods • Deepening of the understanding of intracellular production/packaging mechanisms still ongoing	[80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152]