Table 3. Overview of nanoformulations incorporating cinnamic acid and its derivatives, detailing nanocarrier type, physicochemical characteristics (size, PDI, zeta potential, encapsulation efficiency, and drug loading capacity), target cancer cell lines, and reported therapeutic advantages.

Type of nanocarrier	Type of cinnamic acid derivative	Size (nm)	PDI	ZP (mV)	EE%	DLC%	Target cells	Advantages	Reference
Dextran NPs	Cinnamaldehyde	166.4	∼0.15	∼−16.4	57.6%	21.6	BEAS-2B cells, HUVEC cells, human cardiomyocytes 4910, and HCT-116 cancer cell line	The NPs showed a pH-responsive release with excellent therapeutic performance and significant in vivo safety	52
Cubosomes	Cinnamic acid	N/A	N/A	N/A	N/A	N/A	RAW 264.7 cells and KB cancer cell line	The cubosomes showed higher anticancer activity than free DOX (confirmed by MTT assay) and better cellular uptake (confirmed by flow cytometry assay)	49
Maltodextrin NPs	Cinnamaldehyde	Around 280	Less than 1.2	N/A	N/A	N/A	DU145, SW620, and A549 cancer cell lines	The designed NPs offered a combinational cancer therapy strategy, including oxidative stress inducers and thermal inducers. In vivo, they destroyed cancer in mouse xenograft models	53
SLNs	Ferulic acid	174 ± 5	0.166	−25.9	N/A	N/A	HT-29 and NIH 3T3 cells	SLNs had strong cytotoxic activity with an IC50 of 10 μg mL−1	59
Supramolecular prodrug NPs	Caffeic acid	90–120	N/A	−20 to −26	N/A	N/A	CT26 cells	The NPs showed potent antiproliferative activity, which resulted in a high population of necrotic and apoptotic cells	69
Mannosylated liposomes	Chlorogenic acid	139.0 ± 0.5	<0.3	−25.3 ± 0.8	71.5	N/A	G422 glioma cells	Liposomes potentiated the polarization of TAMs from M2 to M1 phenotype	76
Magnetic (Fe3O4) NPs functionalized with FITC and folic acid	Cinnamaldehyde	10	N/A	−59.6	N/A	N/A	MCF-7, MDAMB-231, and MCF-10A cells	These NPs prolonged circulation time, enhanced hydrophilicity, and sustained the release of cinnamaldehyde. They had an IC50 of 2.84 and 17.44 μg mL−1 against MCF-7 and MDAMB-231, respectively	41
Micelles	Cinnamaldehyde	54.3	0.25	N/A	72.8	10.3%	4T1, A549, and HeLa cell lines	The pH-responsive NPs could induce tumor apoptosis with minimal adverse effects on normal tissues. The IC50 values were determined to be the CPT-equivalent concentrations 4.6, 3.9, and 3.3 μM, respectively, against the three tested cell lines: 4T1 metastatic breast cancer cells, A549, and HeLa cervical cancer cells	54
Carrier-free self-assembled nano drug particles	Cinnamaldehyde	170	0.121	N/A	N/A	N/A	HepG2, H22, and QSG cell lines	Synergistic anticancer effect (antimetabolic activity by 5FU and generation of ROS by cinnamaldehyde). When tested on the H22 murine hepatoma cell line, 5FU–CA NPs had an IC50 of 21.291 μM at 48 hours compared to 66.903 μM for free 5FU and 142.755 μM for free cinnamaldehyde. No significant toxicity was detected on the QSG human hepatocellular cell line	55
pH-sensitive amphiphilic block copolymer NPs	Cinnamaldehyde	N/A	1.33–1.44	N/A	N/A	36.7	A375 and GM cells	The NPs showed a pH-dependent release pattern. They showed enhanced anticancer activity (by cinnamaldehyde and DOX) and promising imaging properties	56
AuNPs	Ferulic acid	34.2 ± 1.3	0.137	−28.5	N/A	N/A	A431 and HaCaT cells	They effectively induced apoptosis, exhibited strong ROS generation, and enhanced caspase-3 activity. The IC50 value was calculated to be 168.7 ± 2.3 μg mL−1	60
Silk fibroin NPs	Rosmarinic acid	255	0.187	−17	39	9.4 ± 0.5	HeLa and MCF-7 cell lines	Rosmarinic silk fibroin NPs had an IC50 of 1.568 and 1.377 mg mL−1 on HeLa and MCF-7, respectively. They were capable of inducing apoptosis besides inhibiting cellular proliferation	73
GO-PEG nanocomposite	Protocatechuic acid and chlorogenic acid	Non-coated and coated NPs: 34 ± 2.4 and 42 ± 3.9	Non-coated and coated NPs: ∼0.28 and ∼0.30	Non-coated and coated NPs: ∼0.30, −17.10 ± 1.072 and −22.72 ± 2.311	Protocatechuic acid and chlorogenic acid in non-coated and coated NPs: 75.23, 72.11, 79.16, and 75.15, respectively	Protocatechuic acid and chlorogenic acid in non-coated and coated NPs: 23.82, 24.47, 19.55, and 23.33, respectively	HDFa and HepG2 cells	Both nanocomposites induced late apoptosis in HepG2 cells with IC50 values of 34.73 ± 1.04 μg mL−1 (non-coated) and 26.79 ± 1.63 μg mL−1 (coated), arrested the cell cycle at the G2/M phase, depolarized mitochondrial membrane potential, and upregulated ROS levels	77
SAL	Chlorogenic acid	90.36 ± 0.54	0.254 ± 0.006	13.8 ± 0.1	49.84	N/A	RAW264.7 and B16F10 cell lines	In the B16F10 cell line, treatment with the modified liposomes resulted in a notable reduction in M2-TAMs and CD4+Foxp3+ T cells, along with an increase in M1-TAMs, CD8+ T cells, and T cell activity, resulting in the enhancement of the tumor inhibition rate	78
C-Fe3O4 NPs@OVA	Chlorogenic acid	52 ± 3	N/A	−34.1	91.56 ± 2.1%	N/A	MDA-MB-231 cancer cell line	C-Fe3O4 NPs@OVA exhibited potent, dose-dependent cytotoxicity with an IC50 of 21 ± 1.74 mg mL−1, suggesting that the nanocarrier is more likely to invade cells than chlorogenic acid alone	79
CLC-DOX NPs	Cinnamaldehyde	338	0.164	N/A	N/A	N/A	HepG2 and H22 cell lines	Only 21% of HepG2 and 51.1% of H22 cells survived after treatment with CLC-DOX NPs, demonstrating their enhanced efficacy in killing cancer cells	57
PLGA NPs	Cinnamic acid	186.3	0.047 ± 0.072 to 0.245 ± 0.089	−28.47	76.98	N/A	MDA-MB-231 cell line	CIN-PLGA-NPs exhibited superiority during in vivo and in vitro evaluation with an IC50 of 0.5171 mM versus 2.296 mM in cells treated with free cinnamic acid	50
Aptamer-conjugated starch NPs	p-Coumaric acid	218.97 ± 3.07	0.299 ± 0.05	29.2 ± 1.35	80.30 ± 0.53	N/A	MDA-MB-231 and NIH3T3 cell lines	The NPs induced cytotoxicity in MDA-MB-231 cells with an IC50 value of 22.56 ± 1.97 μg mL−1 by regulating ROS levels, causing nuclear damage, altering mitochondrial membrane potential, and inducing apoptosis-related protein expression	45
DTX@PCA NPs	p-Coumaric acid	83.4 ± 4.1	∼0.2	−20.4 ± 0.4	33.4 ± 1.3	5.57 ± 0.22	CT26 cell line	DTX@PCA NPs exhibited antiproliferative activity, antimetastatic ability, and enhanced cellular uptake by tumor cells. In vivo, they were characterized by preferential tumor accumulation, prolonged systemic circulation, and reduction of DTX side effects	61
MSNs	Cisplatin acetyl-protected caffeate, acetyl-protected ferulate, and ferulate	200–400 × 600–800	N/A	N/A	70.4, 83.8, and 89.2	7.51, 9.23, and 10.33	BT-474, MCF-7, MDA-MB-468, and HCC1937 cell lines	MTT cytotoxicity assay showed excellent anticancer prospects for all three MSNs, with higher cytotoxicity than cisplatin without causing nephrotoxicity	62
PLGA NPs	Ferulic acid	148 ± 6	N/A	6.63 ± 1.3	73 ± 2	N/A	Only tested in vivo on a breast cancer mouse model	The NPs repressed Notch synergy with Wnt, estrogen, progesterone, HER2 pathways, P-gp level, and reduced the side-effects of DOX and cyclophosphamide	63
Lipidic NCs	Ferulic acid	36.8	0.2	−12.2	89.8	N/A	Caco-2 and HCT-116 cell lines	Ferulic acid lipid NCs had a potent antioxidant, anti-inflammatory, apoptotic, and cytotoxic potential	64
Carbosilane dendrimers	Caffeic acid	215.6–476.4	0.44–0.6	2.7–2.95	N/A	N/A	BJ and A549 cells	Carbosilane dendrimers exhibited low toxicity toward normal BJ fibroblasts and moderate cytotoxicity against A549 cancer cell lines, reducing cell viability by up to 77% compared to the control at a concentration of 100 μM. Additionally, they exhibited robust antioxidant activity that could help to reduce oxidative hemolysis, lipid peroxidation, and ROS levels	70
Magnetic microspheres	Rosmarinic acid	218.44 and 287.58	N/A	Almost 0	50.34	From 0.5 to 1.83	BHK and HepG2 cells	The microspheres demonstrated strong anti-cancer potential against cancer cell lines while sparing normal tissues	74
AgNP-BSA	Chlorogenic acid	96.51	0.265	−17.5	N/A	N/A	DLA cell line	AgNPs-BSA had prominent cytotoxicity to Dalton's lymphoma ascites (DLA) cells with an IC50 of 2.5 μg mL−1, leading to increased ROS levels, and altered levels of oxidized glutathione (GSSG) and reduced glutathione (GSH)	80
Porphyrin-based MOF (PCN-224) NPs	Cinnamaldehyde	90	N/A	−22.5	N/A	N/A	Hela and A549 cell lines	The NPs elevated the level of H2O2, thus improving ROS-mediated cancer cell apoptosis and making PDT/CDT more effective	58
MSNs	Platinum(iv) acetyl-protected and unprotected ferulic acid and cinnamic acid	200–400 × 600–800	N/A	N/A	75–97	8.4, 8.9, and 11.4	MCF-7, BT-474, HCC1937, and MDA-MB-468 cancer cell lines	Overcoming oxaliplatin and cisplatin resistance	65
Chitosan-grafted carbon nanotubes	Caffeic acid	N/A	N/A	N/A	N/A	N/A	MDA-MB-231 cell line	A dose-dependent growth inhibition of the cell line with an IC50 value of 30 μg mL−1 was detected along with increased expression of bax and downregulation of Bcl-2	71
Nanohybrids	Chlorogenic acid	23.8	N/A	N/A	N/A	N/A	Saos-2 cells	Nanohybrids can severely trigger apoptosis and inhibit tumor growth in vivo and in vitro on Saos-2 cells, reducing cell viability to 0.8% at the highest concentration tested	81
Albumin NPs	Chlorogenic acid	20	N/A	N/A	N/A	N/A	MDA-MB-435 cells	The NPs showed an IC50 of 24 μg mL−1 after a 24-hour treatment. A significant increase in the comet tail pattern and a substantial upsurge in early apoptotic cells at 24 hours were observed in the comet assay and annexin-V/FITC/PI flow cytometry, respectively. They also induced a depletion in levels of superoxide dismutase and catalase	44
Zinc oxide NPs	Cinnamic acid	100–200	N/A	N/A	N/A	N/A	KB cells	The obtained NPs showed potent anticancer, antiapoptotic, and antioxidant activity. They resulted in a reduction in cancer cell viability by 97% following their administration	51
Liposomes	p-Coumaric acid	109.6	0.097	−14.3	71.2 ± 0.05	N/A	A375 cell line	IC50 values of the liposomes were determined to be 62.77 μg mL−1 at 24 hours and 55 μg mL−1 at 48 hours. Also, cells treated with the liposome exhibited 5.15% necrosis and 26.96% apoptosis	66
TPGS mixed micelles	Ferulic acid	13.86	Less than 0.25	−6.02	99.89	N/A	Caco-2 cell line	Polymeric micelles had the potential for targeting colon cancer via the miRNA-221/TP53INP1 axis-mediated autophagy. They had an IC50 of 17.1 μg mL−1 and induced cell cycle arrest at the G2/M phase	46
Nanogels	Ferulic acid	59.89 to 89.88	N/A	−0.23 to −0.38	49.32 to 86.81	∼39	HepG2, A549, MCF-7, and HCT-116	pH-responsive ferulic acid-loaded nanogels showed a potent cytotoxic effect. Compared to free ferulic acid, IC50 values were reduced by 58.22%, 78.35%, 45.81%, and 47.94% for HepG2, A549, MCF-7, and HCT-116, respectively	67
Hyalgan-coated polymeric pullulan acetate NPs	Ferulic acid	425 ± 5.2	0.6	−11 ± 2.4	82.6	N/A	Gastrointestinal cancer cell lines (HCT116, AGS, SW620)	The NPs successfully restrained the growth of GIT's cancer cells (HCT-116, AGS, and SW620), achieving IC50 values three times lower than those of free ferulic acid, specifically 55 μg mL−1, 60 μg mL−1, and 110 μg mL−1, respectively	68
Folic acid-functionalized CS NPs	Caffeic acid	157.23 ± 2.64	0.309 ± 0.199	−25.53 ± 2.31	93.42 ± 3.42%	N/A	MCF-7 cell line and tumor-induced rat models	NPs had an IC50 of 40 ± 2.9 μg mL−1 when tested on MCF-7 cancer cells. A downregulation of the biochemical marker of carcinoembryonic antigen and an increased level of superoxide dismutase were spotted	72
Tetrasulfide-based porous organosilica NPs	Rosmarinic acid	50	N/A	−13.53	N/A	58.01	AGS, CT26, HEK-293T, and NIH-3T3 cells	CCK-8 assay showed that administration of NPs containing 140 μg mL−1 of rosmarinic acid killed around 39.2% of AGS gastric cancer cells and 36.9% of CT26 cells after 72 hours	75
SAL	Dox and chlorogenic acid	128.3 ± 0.8	0.164 ± 0.003	−4.33 ± 0.50	DOX: 94.81 ± 0.42 chlorogenic acid: 50.24 ± 2.365	DOX: 2.7 ± 0.03 chlorogenic acid: 0.7 ± 0.003	B16F10 and RAW264.7 cell lines	The MTT assay revealed a reduction in cell survival in a dose-dependent manner. CA-DOX-SAL exerted a stronger activity than each cargo alone	82
PET/Fe3O4@OA NPs	Chlorogenic acid	81.04 ± 1.02	N/A	N/A	N/A	N/A	HCT-116 cells	PET served as a protective barrier, shielding chlorogenic acid from the acidic environment of the GIT. CCK8 assay showed a significantly decreased tumor survival rate and an increased chlorogenic acid-killing effect	13
AgNPs	Caffeic acid	127.6	0.193	−67.8	N/A	N/A	A549 cells	AgNPs showed significant toxicity, with inhibitory effects observed at concentrations of 141 μg mL−1. Cell cycle analysis confirmed NPs' ability to arrest and devastate cancer cells before the synthetic phase	6