Main Research Findings

Doxorubicin (DOX) is a widely used anti-cancer drug, but it has side effects such as cardiotoxicity. 7 , 1 These studies suggest that using low-density lipoprotein (LDL) as a targeted delivery carrier for DOX could potentially improve the delivery efficiency of DOX to tumors and reduce cardiotoxicity. 7 LDL-DOX was found to accumulate more in the liver than free DOX in mice. 7 In contrast, LDL-DOX accumulated less in the heart compared to free DOX. 7 While LDL-DOX showed higher cellular uptake in HepG2 cells compared to DOX alone, it had a weaker anti-proliferative effect on these tumor cells. 7 However, when LDL-DOX or DOX was administered to nude mice bearing HepG2 cells, both drugs demonstrated similar anti-proliferative effects on the tumor cells. 7 Histological analyses revealed that DOX treatment caused disruption of myocardial filaments and vacuolization in the heart compared to the control group, while LDL-DOX treatment did not show any damage to the heart. 7 Furthermore, enzymatic analysis showed that plasma lactate dehydrogenase activity, a common indicator of heart damage, was elevated in the DOX-treated group compared to the control group, while the activity of this enzyme remained unchanged in the LDL-DOX-treated group. 7 The results of this study indicate that LDL could be a promising targeted carrier for DOX as LDL-DOX can exhibit similar anti-proliferative effects as DOX on tumors while reducing DOX-induced cardiotoxicity in the host.

Black phosphorus (BP) nanosheets, with their excellent properties, have been widely used in cancer therapy. 3 BPs are known to form BP nanomaterial-corona complexes in blood, but their biological effects have not been fully explored. 3 In this study, BP-DOX, prepared by loading DOX onto BP nanosheets through electrostatic interaction, was successfully developed for photo-thermal/chemotherapy. 3 BP-DOX demonstrated a tumor inhibition rate of 81.47%, significantly higher than BPs (69.50%) and free DOX (51.91%) in a Hela-bearing mice model due to its pH/photo-responsive controlled drug release property. 3 In vivo experiments showed that BP treatment in healthy mice caused mild inflammation and oxidative stress in the liver and lungs, leading to cell apoptosis. 3 In vitro studies further indicated that BP can induce oxidative stress and metabolic disorders in A549, HepG2, Beas-2B, and LO2 cells. 3 Finally, RGD peptide-conjugated red blood cell (RBC) membrane-coated BPs (RGD-RBC@BP) were prepared using lipid insertion and co-ultrasound methods for efficient tumor-targeted photo-thermal therapy (PTT). 3 RGD-RBC@BP demonstrated positive biocompatibility, photo-thermal properties, and increased cellular uptake by Hela cells, benefiting from the long circulation property of RBCs and RGD peptides. 3 Pharmacokinetic and biodistribution studies of RGD-RBC@BP showed prolonged circulation time and tended to accumulate in tumors overexpressing αvβ3 integrin rather than in the liver after intravenous injection for 24 hours in vivo. 3 Following 808 nm laser irradiation, RGD-RBC@BP nanoparticles exhibited better PTT performance compared to PEGylated BPs (BP-PEG). 3 The active-targeting strategy of biomimetic nanomaterials based on the tumor microenvironment has been proven to have favorable biological prospects in cancer PTT.

Porphyrin-grafted lipid (PGL) nanoparticles encapsulating doxorubicin (DOX) can be used for synergistic chemo-photodynamic therapy (PDT) and fluorescence imaging. 4 PGL nanoparticles can be synthesized using a simple and inexpensive method. 4 DOX can be efficiently loaded into PGL nanoparticles using a pH-gradient loading protocol. 4 PGL-DOX nanoparticles showed excellent cellular uptake and chemo-photodynamic response in different cell lines. 4 Under laser irradiation, cells treated with PGL-DOX nanoparticles at low molar concentrations exhibited a significant reduction in cell viability. 4 Furthermore, in vivo experiments using a xenograft mouse model demonstrated the excellent tumor accumulation capability of PGL-DOX nanoparticles driven by the enhanced permeability and retention (EPR) effect. 4 Fluorescence imaging allowed real-time monitoring of PGL-DOX nanoparticle biodistribution in tumors and major organs in vivo. 4 The combined effects of porphyrin-mediated ROS generation under laser irradiation and the cytotoxic effect of DOX significantly suppressed tumor growth in vivo. 4 The PGL-DOX nanoparticle-based chemo-photodynamic nanoplatform holds potential as a candidate for cancer theranostics.

Benefits and Risks

Benefits Summary

Formulating doxorubicin with lipids could potentially enhance delivery efficiency to tumors and reduce cardiotoxicity. 7 Black phosphorus nanosheets can be used for photothermal therapy and photothermal chemotherapy, offering significant tumor suppression and synergistic effects. 3 Porphyrin-grafted lipid nanoparticles loaded with doxorubicin could achieve synergistic chemo-photodynamic therapy. 4 Treatment using doxorubicin-loaded microbubbles combined with ultrasound might induce cancer cell apoptosis and enhance antitumor effects. 6

Risks Summary

Black phosphorus nanosheets have been shown to cause oxidative stress in the liver and lungs of healthy mice, leading to cell death. 3 Further research is needed to understand the behavior and long-term safety of these nanomaterials in the body.

Comparison Between Studies

Similarities

These studies suggest that formulating doxorubicin with lipids or nanomaterials can potentially enhance delivery to tumors and reduce side effects. They all use in vivo and in vitro experiments to assess the efficacy of these formulations.

Differences

The lipids, nanomaterials, formulation methods, and evaluation methods used in these studies vary. For example, 7 uses LDL as a carrier, while 3 uses black phosphorus nanosheets. 4 focuses on achieving synergistic chemo-photodynamic therapy using porphyrin-grafted lipid nanoparticles.

Consistency and Discrepancies in Results

While these studies suggest the potential of formulating doxorubicin with lipids or nanomaterials to enhance tumor delivery and reduce side effects, direct comparisons of the results are challenging due to the varying lipids, nanomaterials, and formulation methods used. Additionally, these studies are based on animal models, and further research is required to determine their applicability to humans.

Considerations for Real-World Application

These research findings suggest that formulating doxorubicin with lipids or nanomaterials could potentially improve the effectiveness of tumor treatment and reduce side effects. However, more research is needed before these technologies can be used clinically. Safety and efficacy must be confirmed before they can be widely implemented.

Limitations of Current Research

These studies are based on animal models, and more research is needed to determine their applicability to humans. The behavior and long-term safety of these nanomaterials within the body are not yet fully understood. Further research is necessary to confirm the safety and efficacy of these nanomaterials.

Future Research Directions

Clinical trials are needed to confirm the safety and efficacy of these technologies in humans. Further research into the behavior and long-term safety of these nanomaterials in the body is crucial. Developing more efficient formulations and treatment methods requires exploring new lipids and nanomaterials, improving formulation techniques, and developing new evaluation methods.

Conclusion

Formulating doxorubicin with lipids or nanomaterials holds potential for enhancing tumor delivery efficiency and reducing side effects. These technologies offer promising possibilities in cancer treatment, but further research is necessary before they can be applied clinically. Through these studies, we can strive to develop safe and effective delivery systems for doxorubicin and other anticancer drugs to improve the quality of life for cancer patients.