Table 3 Summary of studies outlining using exosomes as targeted drug / and non-coding RNA delivery as a modality for Lung cancer therapy/ treatment

Bovine Milk

Withaferin A, Curcumin, Paclitaxel (PTX) and docetaxel (DTX)

A549, H1299 cancer cells, human normal bronchial epithelial cells (Beas-2B)

Enhanced tumor targetability and tumor reduction by milk-derived drug-loaded exosomes

[219]

Bovine Milk

Paclitaxel (PTX)

A549 lung cancer cells

Augments Antitumor efficacy. Exosomal PTX administered orally exhibited significant tumor growth inhibition against human lung tumor xenografts in mice

[220]

Bovine Milk

Celastrol (CEL)

A549, H1299 NSCLC cells

Enhanced anti-tumor efficacy in NSCLC. Exo-CEL exhibited enhanced anti-tumor efficacy and less toxicity as compared to free CEL, both in vitro and in vivo

[221]

Bovine Milk

si-KRASG12S

A549 lung cancer cells

Dose-dependent anti-proliferative by exosomal siKRASG12S in A549 cells. Significant inhibition of A549 tumor xenografts treated with folic acid-functionalized exosomes carrying siKRAS in vivo and in vitro

[222]

A549 tumor cells derived exosomes

Docetaxel

A549 lung cancer cells

Exo-DTX effectively inhibited A549 cell growth, enhanced cytotoxicity, induced apoptosis, increased ROS production, and demonstrated anti-cancer effects in vitro. In vivo, experiments showed that Exo-DTX could serve as a targeted treatment option with superior drug potency compared to free DTX

[223]

macrophage-derived exosomes (RAW 264.7)

Paclitaxel

Murine Lewis lung carcinoma cell subline (3LL-M27 cells)

Vectorized exosomes, loaded with PTX, exhibited a significant loading capacity and demonstrated a remarkable ability to accumulate in lung cancer cells after systemic administration resulting in improved therapeutic outcomes

[224]

macrophage-derived exosomes) Raw 264.7

Paclitaxel

Cancer cells (MDCKMDR1, MDCKwt, and and (3LL-M27)

Exo-PTX significantly increased cytotoxicity in drug-resistant MDCKMDR1 (Pgp +) cells. The administration of exoPTX resulted in a potent anticancer effect and a high degree of co-localization with cancer cells mouse model of Lewis lung carcinoma pulmonary metastases

[225]

Bovine colostrum-derived exosomes

Paclitaxel

A549 lung cancer cells

ExoPTX exhibited enhanced anti-proliferative activity compared to PAC alone against A549 cells and drug-resistant variants of A549 cells. The oral dose of ExoPAC attached to tumor-targeting ligand folic acid (FA-Exo-PTX) was more effective in inhibiting tumor development in the orthotopic lung cancer model than conventional intravenous administration of PTX

[226]

MDA-MB-231 cells

MiRNA-126

A549 lung cancer cells

miRNA-231-Exo loaded with miRNA-126 inhibited lung cancer cell proliferation and metastasis in mice

[227]

Engineered Exosomes HEK293T

siRNA

A549 lung cancer cells

Targeting siRNA-tLyp-1 exosomes effectively silences cancer cell genes and decreases cancer stem cells' stemness. These engineered exosomes demonstrated high transfection efficiency, making them a promising gene delivery platform for future gene cancer therapy

[228]

Engineered exosomes with PD L-1 antibody

PD-L1siRNA

A549 and H460 lung cancer cells

In vitro, Inhibition of tumor cell proliferation suggests a potential for siRNA as efficient delivery carriers for tumor immunotherapy and gene therapy

[229]

A549 cells (Lung cancer cells derived exosomes

miR-563

A549 lung cancer cells

MiR-563 suppressed the expression of Bcl-2, an anti-apoptotic protein, in A549 cells. This led to increased apoptosis (programmed cell death) in the cells, which resulted in tumor regression and improved survival in vivo

[230]

Engineered exosomes (tLyp-1-modifed EVs)

HEK293T cells

SOX-2-siR1, siR2, siR3

A549 lung cancer cells

Engineered exosomes Inhibited cancer cell growth by Knocking down the expression of the SOX2 gene and decreased the stemness of cancer stem cells in NSCLC

[231]

Human cell-derived exosomes HEK293T cells

miRNA-497

A549 lung cancer cells

Human cell-derived exosomes as carriers for miRNAs cultured in both 2D and 3D microfluidic devices revealed that exosomes loaded with miRNA-497 (miR-497) had potent anti-tumor and anti-angiogenic effects, which effectively inhibited tumor growth and suppressing the expression of associated genes in A549 cells

[157]