Table 1 Engineered EVs for chemotherapy-related combination therapy

Chemotherapy combined with anti-drug resistance treatment

Co-delivery of P-gp siRNA and DOX by engineered EVs

RBC

Mimic vesicles

Incubated with vesicles

P-gp siRNA and DOX

Aptamer modification

Overcame drug resistance and killed MDR tumors

[51]

Tumor cell-derived EVs can directly down-regulate P-gp expression

Bel7402 cells

Biomimetic EVs

Incubated with producing cells

PSINPs loaded with DOX

Possessed cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells

[54]

HEK293T cells

EVs

Incubated with producing cells, the obtained EV were mixed with LipHA

DOX

LipHA modification

Inhibited MDR tumor growth by 89% and extended animal survival time by approximately 50%

[55]

Co-delivery of anti-miRNA and drugs

HCT-116^5FR cell line

Exosomes

Electroporation

MiR21i and 5-FU

Reversed drug resistance and enhanced the cytotoxicity in 5-FU-resistant colon cancer cells

[60]

HEK293T cell culture

Exosomes

Cell transfection

Anti-miR-214

Reversed the resistance to cisplatin in gastric cancer

[61]

4T1 cells

Tumor cell-derived EVs

Anti-miR-21 was transfected to producing cells, the obtained EVs and the GIONs were extruded through 100 nm porous membranes

Anti-miR-214 and GIONs

Attenuated DOX resistance, resulted in effective photothermal effect and demonstrated excellent T2 MR imaging

[62]

Combinational chemo-photothermal therapy

Co-delivery PTA and chemotherapy drugs. Appropriate temperature rise boosted the susceptibility of cancer cells to chemotherapy and reduce their drug resistance

DC2.4

EVs

Incubated with EVs

DOX

Self-grown gold nanoparticles

Improved cellular internalization, controlled drug release, enhanced antitumor efficacy and reduced side effects

[67]

H22 cells

Microparticles

Electroporation

Bi₂Se₃ nanodots and DOX

Resulted in synergistic antitumor efficacy by combining PTT with chemotherapy

[68]

HeLa cells

Microvesicles

Electroporation

ICG and DOX

Almost all the tumor cells could be killed by the synergistic effect of the released DOX and ICG

[69]

4T1 cells

Biomimetic exosomes

Exosomes were mixed with MSNs and then processed through extrusion

ICG and DOX

ICG produced hyperthermia to collapse E-MSNs nanovehicles, achieving effective chemo-photothermal therapy

[70]

Chemotherapy combined with gene therapy

Exosomes as delivery platforms of CRISPR/Cas9

SKOV3 cells

Cancer-derived exosomes

Electroporation

CRISPR/Cas9-targeting PARP-1

Suppressed the expression of PARP-1 and enhanced the chemosensitivity to cisplatin, resulting in the apoptosisof cancer cells

[73]

Co-delivery of therapeutic nucleic acids and chemotherapeutic drugs

Cal 27 cells

Microvesicles

Modified parent cells to get MVs with the membraneodified with biotin and folate, the Bcl-2 siRNA and PTX were packaged into these MVs by electroporation

Bcl-2 siRNA and PTX

Biotin and folate

Enhanced target and synergistic therapy toward breast cancer

[75]

Combinational delivery of nanoparticles and drugs

Modified chemotherapeutics-loaded NPs by using EV membrane

MDA-MB-231 cells

Biomimetic exosomes

The mixture of PCNPs and exosome membrane was coextruded by a 220 nm polycarbonate porous membrane

PTX-S-LA and CuB loaded PEG-PCL NPs

Enhanced breast cancer metastasis inhibition

[81]

Patient’s urine

Biomimetic exosomes

Electroporation

PMA/Fe-HSA @DOX

Achieved superior synergistic low-dose chemo/chemodynamic performance g

[39]

Macrophages

Biomimetic exosomes

Exosomes were mixed with PLGA and coextruded through a 100 nm membrane, then peptides were decorated on the exosomal membrane

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded DOX

Peptides that can target tumor cells

Exhibited tumor-targeting efficacy, inhibited tumor growth and induced intense tumor apoptosis

[82]