Table 2.

Summary of strengths and weaknesses of delivery systems.

Delivery System	Strengths	Weaknesses	Source Publications
Platelets	Readily available and biocompatible Easily activated to release drugs Preferred homing to wounds/injury sites make platelets ideal candidate for post-surgical drug delivery to surgical sites High loading efficacy Easy surface modifications Encapsulated drugs are protected from physical stress and immune system Controlled release from platelets can be achieved by induction with agonists	Platelets can be easily deformed and aggregated Complex ex vivo processing for loading of therapeutics Agents used to prevent platelet aggregation can be harmful to human body Limitations with storage Unexpected activation and release of therapeutics may occur in unintended sites	[83,85,86,140,141,142,143,144]
DMAbs	Robust expression in vivo Transient expression Well tolerated and little risk of integration Inexpensive to produce and can be administered repeatedly Deemed safe in early clinical studies	Pain associated with site of electroporation Low efficiency in large animals/humans Restricted to protein therapeutics Induction of antibodies against DNA is possible	[110,145,146,147,148,149]
Viral Vectors	Stimulates immune system Can be easily genetically engineered for tumor targeting Can target both dividing and non-dividing cells Can be engineered for selective replication in target cells High levels of expression of the therapeutics for prolonged period Capacity for incorporating multiple genes simultaneously Potential for systemic delivery	Risk of restored virulence and seroconversion in vivo Anti-viral responses may limit efficacy and dosing Complex engineering process to avoid interference by pre-existing immunity High safety and regulatory standards Risks of random integration and oncogene activation	[90,150,151,152,153,154]
Extracellular Matrix Binding Protein	Efficient targeting of the whole TME (cancer cells and supporting cells) Prolonged tissue retention of the therapeutics	Selection of tumor-restricted ECM might be challenging Limited information on stability and efficacy for systemic administration	[132,155]
Bacteria	Preferred accumulation and proliferation in tumor tissues Ability to penetrate tissues Expression of chemotactic receptors for migration to TME Can be easily genetically engineered to carry various therapeutics and targeting moieties Modifiable promotors that respond to different agents (small molecules, radiation, etc.) Ability to stimulate immune system Potential for oral delivery	Residual bacterial virulence might be an issue in immunocompromised patients Effective colonization and targeting may not be achieved in small metastatic lesions Concerns of genetic instability, mutations, and horizontal gene transfers Existing immunity against the bacterial vectors may reduce efficacy	[120,123,128,156,157,158,159]
Hydrogels	Easy drug encapsulation and protection of therapeutics from degradation by enzymes, low pH, etc. Biocompatible and biodegradable Tunable shape and mesh size for controlled release of drugs Prolonged retention; localized and sustained drug release Low likelihood of systemic toxicity Low cost of preparation Minimally invasive (injectable) Potential for oral delivery	Issues with viscosity Poor mechanical stability Difficult to sterilize Issues of biocompatibility with synthetic hydrogels Limitations with encapsulation and delivery of hydrophobic drugs	[136,137,138,160,161,162,163,164]

DMAbs: DNA-encoded Monoclonal Antibodies; TME: Tumor microenvironment.