Polypeptide for targeted destruction of lipid droplets and application of polypeptide in preparation of antitumor drugs

Abstract

The invention relates to a polypeptide for targeted destruction of lipid droplets and application of the polypeptide in preparation of antitumor drugs, and belongs to the technical field of biological drug manufacturing. In order to solve the problem that an existing anti-tumor drug aiming at tumor lipid droplets cannot effectively inhibit immune escape of tumor cells while destroying the lipid droplets, the invention provides a polypeptide for targeted destruction of the lipid droplets, and the polypeptide comprises a PLIN2 targeted peptide fragment, a self-assembly peptide fragment, an enzyme response peptide fragment and an HLA-E targeted peptide fragment which are connected in sequence. On the basis of a double-targeting strategy, the polypeptide for targeted destruction of the lipid droplets is constructed, and the polypeptide can target the PLIN2 protein on the surfaces of the lipid droplets; the self-assembled peptide fragment can form a nanofiber structure on the surface of the lipid droplet, the structure and function of the lipid droplet are destroyed, endoplasmic reticulum stress is caused, and tumor cell immunogenicity death is caused. The HLA-E targeting peptide fragment released by polypeptide digestion can specifically target HLA-E on a tumor cell membrane, block an NKG2A-HLA-E pathway, and effectively inhibit immune escape of tumor cells.

Description

Technical Field

[0001] The present invention belongs to the technical field of biopharmaceutical manufacturing, and in particular relates to a polypeptide for targeted destruction of lipid droplets and its application in the preparation of anti-tumor drugs. Background Art

[0002] Lipid droplets are dynamic, ubiquitous lipid storage organelles within cells, composed of triglycerides and cholesterol esters encapsulated by a single phospholipid membrane. In recent years, studies have revealed that lipid droplets play a key role in tumor metabolic reprogramming, metastasis, therapeutic resistance, and immune escape, making them a new focus of cancer research. During energy metabolism, tumor cells rely on fatty acids stored in lipid droplets to meet the energy needs of rapid proliferation. Under conditions of hypoxia or nutrient deprivation, lipid droplets provide free fatty acids through lipolysis to fuel tumor physiological activities. Furthermore, lipid droplets act as buffers against lipid peroxidation, preventing ferroptosis of tumor cells caused by lipid peroxidation.

[0003] Disruption of the lipid droplet structure in tumor cells leads to the release of large amounts of free fatty acids, which induce endoplasmic reticulum stress by disrupting the endoplasmic reticulum structure and calcium ion homeostasis in tumor cells. Endoplasmic reticulum stress can trigger the immunogenic death of tumor cells, transforming them from non-immunogenic to immunogenic, thereby mediating the body's anti-tumor immune response.

[0004] However, in order to mediate immune escape, tumor cells upregulate the expression of HLA-E molecules on their cell surfaces, enabling them to bind to the inhibitory receptor NKG2A on the surfaces of NK cells and some T cells, forming the NKG2A-HLA-E axis. This inhibits the activity of NK cells and T cells, resulting in a weakened response to the immunogenic cell death of tumor cells. This means that even if tumor cells undergo immunogenic cell death, immune cells may not be able to effectively recognize and eliminate these dead tumor cells, leading to tumor recurrence, metastasis, and immune escape, compromising treatment efficacy.

[0005] PLIN2, a key member of the lipid droplet surface coating protein family, is primarily localized to the lipid droplet membrane and plays a central role in lipid droplet formation, stability, and metabolic regulation. Its expression level is closely correlated with the number of intracellular lipid droplets and is abnormally upregulated in various metabolic diseases and tumors. Studies have demonstrated that knocking down PLIN2 can reduce lipid droplet stability and increase its susceptibility to rupture. However, this approach is technically challenging and has a limited mechanism of action, failing to effectively disrupt lipid droplets while simultaneously addressing the immune evasion of tumor cells. Summary of the Invention

[0006] To address the problem that existing anti-tumor drugs targeting tumor lipid droplets cannot effectively inhibit the immune escape of tumor cells while destroying lipid droplets, the present invention provides a polypeptide that targets the destruction of lipid droplets and its use in the preparation of anti-tumor drugs. The polypeptide triggers endoplasmic reticulum stress by specifically destroying tumor cell lipid droplets, thereby inducing immunogenic death of tumor cells; at the same time, by blocking the NKG2A-HLA-E axis, the activity of NK cells and T cells is increased, further promoting the immune killing of tumors and improving the effect of immunotherapy.

[0007] The technical solution of the present invention:

[0008] A polypeptide for targeted destruction of lipid droplets, comprising a PLIN2 targeting peptide, a self-assembling peptide, an enzyme-responsive peptide, and an HLA-E targeting peptide connected in sequence, wherein the amino acid sequence of the PLIN2 targeting peptide is shown in SEQ ID No. 1; the amino acid sequence of the self-assembling peptide is shown in SEQ ID No. 2; the amino acid sequence of the enzyme-responsive peptide is shown in SEQ ID No. 3; and the amino acid sequence of the HLA-E targeting peptide is shown in SEQ ID No. 4.

[0009] Furthermore, the molecular structure of the polypeptide that targets and destroys lipid droplets is shown in Formula I:

[0010]

[0011] Formula I.

[0012] Furthermore, the preparation method of the polypeptide targeted for destroying lipid droplets adopts a polypeptide solid-phase synthesis method, and the required amino acids in the PLIN2 targeting peptide segment, the self-assembling peptide segment, the enzyme response peptide segment and the HLA-E targeting peptide segment sequence are sequentially connected through amide bonds from the C-terminus to the N-terminus to obtain an artificially synthesized polypeptide targeted for destroying lipid droplets.

[0013] Application of a polypeptide for targeted destruction of lipid droplets in the preparation of anti-tumor drugs.

[0014] Furthermore, the tumors include renal cancer, breast cancer and liver cancer.

[0015] Furthermore, the anti-tumor drug has a polypeptide that targets and destroys lipid droplets as the only active ingredient or one of the active ingredients.

[0016] Furthermore, the anti-tumor drug is a parenteral dosage form, specifically an injectable dosage form.

[0017] Furthermore, the anti-tumor drug can specifically recognize and bind to the PLIN2 protein on the surface of lipid droplets, thereby destroying the structure and function of lipid droplets.

[0018] Furthermore, the anti-tumor drug specifically recognizes and binds to the HLA-E protein on the surface of tumor cells, thereby blocking the NKG2A-HLA-E pathway and inhibiting immune escape.

[0019] Beneficial effects of the present invention:

[0020] This invention constructs a peptide targeting system for lipid droplet destruction based on a dual-targeting strategy. Among the peptides targeting lipid droplets, the PLIN2-targeting peptide possesses lipid droplet-specific targeting capabilities, accurately recognizing and binding to the PLIN2 protein on the lipid droplet surface, enabling in situ peptide enrichment in tumors. The self-assembling peptide forms nanofiber structures on the lipid droplet surface, allowing it to remain on the surface for extended periods, disrupting the lipid droplet structure and function, leading to endoplasmic reticulum stress in tumor cells and immunogenic cell death. The enzyme-responsive peptide is specifically cleaved by matrix metalloproteinases (MMP-2) in the tumor microenvironment, releasing the HLA-E-targeting peptide from the peptide. The HLA-E-targeting peptide specifically targets HLA-E on the tumor cell membrane, blocking the NKG2A-HLA-E pathway, enhancing NK cell and T cell activity, effectively inhibiting tumor cell immune escape, and promoting immune killing of tumors.

[0021] The present invention provides a combined treatment scheme that utilizes polypeptides to target PLIN2 to destroy lipid droplets while blocking the NKG2A-HLA-E pathway to enhance anti-tumor immunity. It has a broad-spectrum anti-tumor effect and shows broad clinical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Schematic diagram of the molecular structure of the polypeptide LTN for targeted destruction of lipid droplets in Example 1;

[0023] Figure 2 This is a comparison of fluorescence signals at different administration times in the mouse model injected with LTN and LTN-C in Example 2;

[0024] Figure 3 Figures 2 and 3 are Oil red staining and BODIPY staining images of Renca cells co-cultured with LTN and LTN-C in Example 3, with A being the Oil red staining image and B being the BODIPY staining image;

[0025] Figure 4 This is a laser confocal microscopic image of renal cancer Renca cells co-cultured with LTN and LTN-C after ER-Tracker Red staining in Example 4;

[0026] Figure 5 These are the staining images of the migration and invasion experiments of renal cancer Renca cells after treatment with LTN and LTN-C in Example 5. The upper layer is the staining image of the migration experiment, and the lower layer is the staining image of the invasion experiment;

[0027] Figure 6 This is a comparison of ATP levels in the supernatant of renal cancer Renca cells after treatment with LTN and LTN-C in Example 6;

[0028] Figure 7 These are DAPI staining images of CRT and HMGB1 detection in renal cancer Renca cells after treatment with LTN and LTN-C in Example 6, A for CRT detection, and B for HMGB1 detection;

[0029] Figure 8 CD107a in T cells and NK cells after treatment with LTN and LTN-C in Example 7 + Cell ratio comparison chart, A is the representative cell CD8 of T cells + Cells, B is a representative cell of NK cells CD56 + cell;

[0030] Figure 9 This is a comparison of cell viability of mouse breast cancer cells and liver cancer cells after treatment with LTN and LTN-C in Example 8, A is breast cancer cells, and B is liver cancer cells. DETAILED DESCRIPTION

[0031] The technical solution of the present invention is further described below with reference to the embodiments, but is not limited thereto. Any modification or equivalent replacement of the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention shall be included in the scope of protection of the present invention. The process equipment or devices not specifically noted in the following examples are all conventional equipment or devices in the art. Unless otherwise specified, the raw materials used in the examples of the present invention can be obtained commercially; unless otherwise specified, the technical means used in the examples of the present invention are all conventional means well known to those skilled in the art.

[0032] Example 1

[0033] This embodiment provides a polypeptide for targeted destruction of lipid droplets and a method for preparing the same.

[0034] In this embodiment, the polypeptide LTN targeting lipid droplet destruction is composed of a PLIN2 targeting peptide segment, a self-assembling peptide segment, an enzyme response peptide segment, and an HLA-E targeting peptide segment connected in sequence. The molecular structure diagram is shown in FIG. Figure 1 The amino acid sequence of the PLIN2 targeting peptide is shown in SEQ ID No. 1, specifically ACNIYGAQGC; the amino acid sequence of the self-assembling peptide is shown in SEQ ID No. 2, specifically KLVFF; the amino acid sequence of the enzyme response peptide is shown in SEQ ID No. 3, specifically GPLGVRG; the amino acid sequence of the HLA-E targeting peptide is shown in SEQ ID No. 4, specifically VMPLSAPTL.

[0035] Among the peptides LTN that target and destroy lipid droplets, the PLIN2 targeting peptide has lipid droplet-specific targeting function; the self-assembling peptide can form a nanofiber structure on the surface of lipid droplets and can remain on the surface of lipid droplets for a long time, destroying the structure and function of lipid droplets, leading to endoplasmic reticulum stress of tumor cells and causing immunogenic death of tumor cells; the enzyme-responsive peptide can be specifically cleaved by matrix metalloproteinase (MMP-2) in the tumor microenvironment, releasing the HLA-E targeting peptide from the peptide. The HLA-E targeting peptide can specifically target HLA-E on the tumor cell membrane, blocking the NKG2A-HLA-E pathway, enhancing the activity of NK cells and T cells, and promoting immune killing of tumors.

[0036] The polypeptide LTN targeted to destroy lipid droplets provided in this embodiment is synthesized by conventional solid phase synthesis of polypeptides in the art from C

[0037] The amino acids required in the PLIN2 targeting peptide, the self-assembling peptide, the enzyme-responsive peptide, and the HLA-E targeting peptide sequence are sequentially connected from end to N-terminus through amide bonds to obtain an artificially synthesized lipid droplet-destroying polypeptide LTN, whose molecular structure is shown in Formula I:

[0038]

[0039] Formula I.

[0040] This example also provides a non-conformably self-assembling control polypeptide LTN-C, which is composed of a PLIN2 targeting peptide, a non-conformably self-assembling peptide, an enzyme response peptide, and an HLA-E targeting peptide connected in sequence; wherein the amino acid sequence of the PLIN2 targeting peptide is shown in SEQ ID No. 1, specifically ACNIYGAQGC; the amino acid sequence of the non-conformably self-assembling peptide is shown in SEQ ID No. 5, specifically KAAGG; the amino acid sequence of the enzyme response peptide is shown in SEQ ID No. 3, specifically GPLGVRG; and the amino acid sequence of the HLA-E targeting peptide is shown in SEQ ID No. 4, specifically VMPLSAPTL.

[0041] The control peptide LTN-C is synthesized by conventional solid-phase peptide synthesis methods in the art. The required amino acids in the PLIN2 targeting peptide, the invariant peptide, the enzyme-responsive peptide, and the HLA-E targeting peptide sequence are sequentially linked from the C-terminus to the N-terminus through amide bonds to obtain an artificially synthesized control peptide LTN-C. Its molecular structure is shown in II:

[0042]

[0043] Formula II.

[0044] Example 2

[0045] This example demonstrates that the polypeptide LTN, which targets and destroys lipid droplets, has the ability to be targeted in vivo and retained in tumors.

[0046] In order to evaluate the in vivo targeting and tumor retention abilities of the lipid droplet-targeting and destruction polypeptide LTN and the control polypeptide LTN-C obtained in Example 1, a mouse tumor model was established in this example.

[0047] Four-week-old female BALB / c mice were selected for in vivo experiments. Renca cells (5 × 10 6 After the small animal model was successfully established, LTN and LTN-C were injected into the tail vein of the mice with an injection volume of 200 μL and 400×10⁻ cells. 6 M, In vivo imaging systems (IVIS) were used to capture the fluorescence signals at 4, 8, 12, 24, 48, and 72 hours after injection.

[0048] The results are as follows Figure 2 As shown, LTN is primarily distributed at the tumor site, indicating that it can precisely target mouse tumors in vivo and retain them for a long time. LTN-C can also precisely target tumors, but its retention time in vivo is shorter. This suggests that the PLIN2-targeting peptides in LTN and LTN-C have good PLIN2 targeting properties, enabling drug accumulation on the surface of tumor cell lipid droplets. The self-assembling peptides in LTN form nanofiber structures on the surface of lipid droplets, securing the peptides there and prolonging drug retention.

[0049] Example 3

[0050] This example demonstrates that the polypeptide LTN, which targets and destroys lipid droplets, has the effect of destroying lipid droplets in tumor cells.

[0051] To evaluate the effect of the lipid droplet-targeting peptide LTN on lipid droplets in tumor cells, Renca renal cancer cells in good condition and growing logarithmically were seeded in confocal microplate culture dishes. After the cells adhered, LTN and LTN-C (as described in Example 1) were added at a concentration of 20 μmol / L and co-cultured with PBS for one day. The cell culture medium was then removed, and the cells were fixed with Oil Red O fixative. The cells were washed twice with distilled water, rinsed with 60% isopropanol, and then freshly prepared Oil Red O staining solution was added. The cells were counterstained with Mayer's hematoxylin solution, and then incubated with Oil Red O buffer until the nuclei turned blue. The cells were then observed under a microscope. For BODIPY staining, the cells to be tested were removed, washed twice with PBS, the PBS was aspirated, and the cells were fixed with 4% paraformaldehyde fixative at room temperature for 10-15 minutes. After fixation, the cells were washed 1-2 times with PBS. The PBS was aspirated, and an appropriate volume of Staining Solution was added. The cells were incubated in the dark at room temperature for 10-20 minutes, and then washed twice with PBS. Fluorescence microscopy was used to observe green fluorescence using an excitation wavelength of approximately 488 nm.

[0052] The results are as follows Figure 3 As shown, compared with the PBS control, LTN-C had no significant effect on lipid droplets in tumor cells, but after LTN treatment, lipid droplets in tumor cells were significantly reduced and fluorescence decreased, thus proving that the lipid droplet-targeting peptide LTN has a destructive effect on lipid droplets in tumor cells.

[0053] Example 4

[0054] This example demonstrates that the polypeptide LTN, which targets and destroys lipid droplets, has the effect of inducing endoplasmic reticulum stress in tumor cells.

[0055] To evaluate the effects of the lipid droplet-targeting peptide LTN on ER stress in tumor cells, Renca renal cancer cells, growing logarithmically and in good condition, were seeded in confocal microscopy culture dishes. After the cells adhered, LTN and LTN-C (from Example 1) were added at a concentration of 20 μmol / L, followed by PBS solution, and incubated for one day. ER-Tracker Red staining solution, pre-incubated at 37°C, was then added and incubated with the cells for 30 minutes. The ER-Tracker Red staining solution was removed, and the cells were washed one to two times with cell culture medium. The cells were then observed using a laser confocal microscope.

[0056] The results are as follows Figure 4 As shown in the figure, compared with the PBS control and LTN-C, the ER fluorescence signal of tumor cells was significantly enhanced after LTN treatment, indicating that LTN induced ER stress in tumor cells.

[0057] Example 5

[0058] This example demonstrates that the polypeptide LTN, which targets and destroys lipid droplets, has the effect of inhibiting tumor cell migration and invasion.

[0059] In order to evaluate the effect of lipid droplet-targeting peptide LTN on tumor cell migration and invasion, in the invasion experiment, Matrigel was spread in the upper chamber of Transwell chamber, and Renca cells in good condition and logarithmically growing were plated at 10 cells per well. 5 Cells were seeded at a density of 100 μL in the upper chamber of a Transwell containing a 20 μmol / L solution of LTN and LTN-C obtained in Example 1 and PBS. 750 μL of 1640 complete medium was added to the lower chamber. After 48 hours of incubation at 37°C, the invaded cells in the lower layer were stained and counted. For the migration assay, Transwell inserts were placed in 24-well plates. Serum-free medium and tumor cells were added directly to the upper chamber of each Transwell. A 20 μmol / L solution of LTN and LTN-C obtained in Example 1 and PBS were also added. 750 μL of 1640 complete medium was added to the lower chamber. After 48 hours of incubation at 37°C, the invaded cells in the lower layer were stained and counted.

[0060] The results are as follows Figure 5 As shown in the figure, compared with the PBS control and LTN-C, the number of tumor cell migration and invasion was reduced after LTN treatment. This indicates that LTN destroys the lipid droplets of tumor cells, causing them to lose the energy supply required for migration and invasion, thereby inhibiting tumor cell migration and invasion.

[0061] Example 6

[0062] This example demonstrates that the polypeptide LTN, which targets and destroys lipid droplets, has the effect of triggering the immunogenic death of tumor cells.

[0063] In order to evaluate the effect of the lipid droplet-targeting peptide LTN on the immunogenic death of tumor cells, Renca renal cancer cells in good logarithmic growth were inoculated in a confocal cell culture dish. After the cells adhered, LTN and LTN-C obtained in Example 1 were added at a concentration of 20 μmol / L and co-cultured with PBS for 1 day.

[0064] For ATP detection, the cell supernatant was first collected and centrifuged at 12,000 rpm for 5 min at 4°C. The secreted ATP content was determined using an ATP bioluminescence assay kit.

[0065] For CRT (calreticulin) and HMGB1 (high-mobility group box 1) detection, cells were first fixed with 4% paraformaldehyde for 15 minutes. Cells were then incubated with 0.3% Triton X-100 for 5 minutes at room temperature and washed. Cells were then incubated with bovine serum albumin for 1 hour at 37°C, followed by incubation with CRT or HMGB1 monoclonal antibodies, washed three times with PBS, and incubated with fluorescent secondary antibodies for 1 hour. Finally, cells were stained with DAPI (4',6-diamidino-2-phenylindole) and observed using a laser confocal microscope.

[0066] The results are as follows Figure 6 and Figure 7 As shown, compared with the PBS control and LTN-C, LTN-treated tumor cells showed the highest ATP levels in the supernatant, increased CRT expression within the tumor cells, and decreased HMGB1 in the nucleus. This indicates that LTN-treated tumor cells undergo immunogenic cell death. However, LTN-C, which cannot self-assemble into nanofiber structures on the surface of lipid droplets, is unable to disrupt lipid droplet structure and function, thereby failing to induce ER stress and immunogenic cell death. This demonstrates that LTN can trigger immunogenic cell death by disrupting the structure and function of tumor cell lipid droplets.

[0067] Example 7

[0068] This example demonstrates that the polypeptide LTN, which targets and destroys lipid droplets, has the ability to enhance the activity of NK cells and T cells.

[0069] To evaluate the effects of the lipid droplet-targeting peptide LTN on NK and T cell activity, PBMCs (peripheral blood mononuclear cells) were seeded into 12-well plates and cocultured with Renca renal cancer cells in RPMI-1640 medium supplemented with IL-12 for one day. Subsequently, a 20 μmol / L solution of LTN and LTN-C (Example 1) and PBS was added to the culture medium. After one day, the cells were harvested and incubated with the respective antibodies in the dark for 30 minutes. After washing twice with PBS, the cells were resuspended in 300 μL of cold PBS and analyzed by flow cytometry.

[0070] The results are as follows Figure 8 As shown, CD107a + The cells are NK cells and CD8 + CD8, a marker of T cell activation + The cells are representative cells of T cells, CD56 + The cells are representative cells of NK cells. CD107a + The increase in the proportion of cells indicates that NK cells and CD8 +The activity of T cells was enhanced accordingly. Compared with the PBS control, the NK cells and CD8 + CD107a in T cells + The cell percentages showed an upward trend, indicating that both LTN and LTN-C can be enzymatically hydrolyzed by MMP-2 in tumor cells. The HLA-E-targeting peptide released from the polypeptide can bind to HLA-E on the tumor cell membrane, blocking the NKG2A-HLA-E pathway and enhancing the activity of NK cells and T cells. Compared with LTN-C, LTN has a more significant effect on promoting the vitality of immune cells. This is because LTN itself has the ability to destroy tumor lipid droplets, which can cause immunogenic death of tumor cells and activate NK cells and T cells. Blocking the NKG2A-HLA-E pathway further enhances the anti-tumor effect of immune cells.

[0071] Example 8

[0072] This example demonstrates that the lipid droplet-targeting polypeptide LTN has an inhibitory effect on the cell viability of breast cancer cells and liver cancer cells.

[0073] Well-developed, logarithmically growing mouse breast cancer cell line 4T1 and mouse hepatocellular carcinoma cell line H22 were used. After the cells adhered, 20 μmol / L of LTN and LTN-C (Example 1) and PBS solutions were added. The cells were then co-cultured in a 37°C cell culture incubator. After 48 hours, the culture medium was discarded and fresh culture medium containing 90 μL of serum-free culture medium and 10 μL of CCK-8 solution was added for 4 hours. Finally, the absorbance was measured using a microplate reader.

[0074] The results are as follows Figure 9 As shown, compared with the PBS control and LTN-C, the activity of breast cancer cells and liver cancer cells after LTN treatment was significantly reduced, thereby demonstrating that the polypeptide for targeted destruction of lipid droplets provided by the present invention has wide applicability in cancer treatment.

Claims

1. A polypeptide for targeting and destroying lipid droplets, characterized in that: The invention comprises a PLIN2 targeting peptide, a self-assembling peptide, an enzyme response peptide and an HLA-E targeting peptide connected in sequence, wherein the amino acid sequence of the PLIN2 targeting peptide is shown in SEQ ID No. 1; the amino acid sequence of the self-assembling peptide is shown in SEQ ID No. 2; the amino acid sequence of the enzyme response peptide is shown in SEQ ID No. 3; and the amino acid sequence of the HLA-E targeting peptide is shown in SEQ ID No.

4.

2. The polypeptide for targeting and destroying lipid droplets according to claim 1, characterized in that The molecular structure of the polypeptide targeting lipid droplet destruction is shown in Formula I: Formula I.

3. The polypeptide for targeting and destroying lipid droplets according to claim 1 or 2, characterized in that The preparation method of the polypeptide targeted at destroying lipid droplets adopts a polypeptide solid-phase synthesis method, and the required amino acids in the PLIN2 targeting peptide segment, the self-assembling peptide segment, the enzyme response peptide segment and the HLA-E targeting peptide segment sequence are sequentially connected through amide bonds from the C-terminus to the N-terminus to obtain an artificially synthesized polypeptide targeted at destroying lipid droplets.

4. Use of the polypeptide for targeted destruction of lipid droplets according to any one of claims 1 to 3 in the preparation of anti-tumor drugs.

5. The use of the polypeptide for targeting and destroying lipid droplets according to claim 4 in the preparation of anti-tumor drugs, characterized in that: The tumors include kidney cancer, breast cancer and liver cancer.

6. Use of the polypeptide for targeted destruction of lipid droplets according to claim 5 in the preparation of anti-tumor drugs, characterized in that: The anti-tumor drug has a polypeptide that targets and destroys lipid droplets as the only active ingredient or one of the active ingredients.

7. Use of the polypeptide for targeted destruction of lipid droplets according to claim 6 in the preparation of anti-tumor drugs, characterized in that: The anti-tumor drug is in a parenteral administration form, specifically an injection administration form.

8. Use of the polypeptide for targeted destruction of lipid droplets according to claim 7 in the preparation of anti-tumor drugs, characterized in that: The anti-tumor drug can specifically recognize and bind to the PLIN2 protein on the surface of the lipid droplet, thereby destroying the structure and function of the lipid droplet.

9. Use of the polypeptide for targeted destruction of lipid droplets according to claim 8 in the preparation of anti-tumor drugs, characterized in that: The anti-tumor drug specifically recognizes and binds to the HLA-E protein on the surface of tumor cells, blocks the NKG2A-HLA-E pathway, and inhibits immune escape.

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